Kastin Handbook of Biologically Active Peptides

1. Auflage 2011
ISBN: 978-0-08-046379-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 1640 Seiten

Peptides play a crucial role in many physiological processes including actions as neurotransmitters, hormones, and antibiotics. Research has shown their importance in such fields as neuroscience, immunology, pharmacology, and cell biology. The Handbook of Biologically Active Peptides presents, for the first time, this tremendous body of knowledge in the field of biologically active peptides in one single reference. The section editors and contributors represent some of the most sophisticated and distinguished scientists working in basic sciences and clinical medicine. The Handbook of Biologically Active Peptides is a definitive, all-encompassing reference that will be indispensable for individuals ranging from peptide researchers, to biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and to endocrinologists. Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas with which they would not ordinarily be familiar.*Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas that they would not ordinarily be familiar.*Fascinating relationships described in the book include the presence of some peptides originally found in frog skin that persist in the human human and brain where they can affect food intake and obesity.

Autoren/Hrsg.

Kastin, Abba

Kastin, Abba J.

Inhaltsverzeichnis

1;Front cover;1
2;Title page;5
3;Copyright page;6
4;Table of contents;7
5;Contributors;21
6;Preface;41
7;Foreword;45
8;I: Plant Peptides Section;47
8.1;1: 4-kDa Peptide;47
8.1.1;ABSTRACT;47
8.1.2;DISCOVERY;47
8.1.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;47
8.1.4;DISTRIBUTION OF THE mRNA;47
8.1.5;PROCESSING;48
8.1.6;RECEPTORS;48
8.1.7;ACTIVE AND/OR SOLUTION CONFORMATION;48
8.1.8;BIOLOGICAL ACTIONS;48
8.1.9;References;50
8.2;2: AtPep1 Peptides;51
8.2.1;ABSTRACT;51
8.2.2;DISCOVERY;51
8.2.3;STRUCTURE OF AtPep1 AND THE GENE ENCODING THE PRECURSOR PROTEIN ProAtPep1;51
8.2.4;DISTRIBUTION OF ProAtPep1 mRNA;52
8.2.5;PROCESSING OF ProAtPep1;53
8.2.6;AtPep1 RECEPTOR;53
8.2.7;SOLUTION CONFORMATION;53
8.2.8;BIOLOGICAL ACTIONS OF AtPep1;53
8.2.9;Acknowledgments;54
8.2.10;References;54
8.3;3: CLAVATA3: A Putative Peptide Ligand Controlling Arabidopsis Stem Cell Specification;55
8.3.1;ABSTRACT;55
8.3.2;DISCOVERY;55
8.3.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;56
8.3.4;RECEPTORS;58
8.3.5;BIOLOGICAL ACTIONS;59
8.3.6;References;60
8.4;4: DVL Peptides Are Involved in Plant Development;63
8.4.1;ABSTRACT;63
8.4.2;DISCOVERY;63
8.4.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;64
8.4.4;DISTRIBUTION OF THE DVL1 mRNA;64
8.4.5;PROCESSING;65
8.4.6;RECEPTORS;66
8.4.7;BIOLOGICAL ACTION;66
8.4.8;References;67
8.5;5: The POLARIS Peptide;69
8.5.1;ABSTRACT;69
8.5.2;DISCOVERY;69
8.5.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;71
8.5.4;DISTRIBUTION OF THE mRNA;71
8.5.5;PROCESSING;72
8.5.6;BIOLOGICAL ACTIONS;72
8.5.7;References;73
8.6;6: Phytosulfokine;75
8.6.1;ABSTRACT;75
8.6.2;INTRODUCTION;75
8.6.3;DISCOVERY AND BIOLOGICAL ACTIONS;75
8.6.4;STRUCTURE OF THE PRECURSOR mRNA/GENE;76
8.6.5;TYROSINE SULFATION;77
8.6.6;RECEPTORS;77
8.6.7;CONCLUSION;77
8.6.8;Acknowledgments;78
8.6.9;References;78
8.7;7: RALF Peptides;79
8.7.1;ABSTRACT;79
8.7.2;DISCOVERY;79
8.7.3;STRUCTURE OF THE RALF PEPTIDE AND ITS PRECURSOR cDNA AND GENE;79
8.7.4;DISTRIBUTION OF THE mRNA;80
8.7.5;PROCESSING;80
8.7.6;RECEPTOR;80
8.7.7;SOLUTION CONFORMATION OF RALF;81
8.7.8;BIOLOGICAL ACTION OF RALF;81
8.7.9;Acknowledgment;81
8.7.10;References;82
8.8;8: ROTUNDIFOLIA4: A Plant-Specific Small Peptide;83
8.8.1;ABSTRACT;83
8.8.2;DISCOVERY;83
8.8.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;83
8.8.4;DISTRIBUTION OF THE mRNA;84
8.8.5;PROCESSING;84
8.8.6;RECEPTORS;85
8.8.7;BIOLOGICAL ACTIONS;85
8.8.8;References;86
8.9;9: The S-Locus Cysteine-Rich Peptide SCR/SP11;87
8.9.1;ABSTRACT;87
8.9.2;DISCOVERY OF SCR;87
8.9.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;89
8.9.4;DISTRIBUTION OF THE mRNA;89
8.9.5;PROCESSING OF THE SCR PROTEIN;90
8.9.6;THE SCR RECEPTOR;90
8.9.7;STRUCTURE;90
8.9.8;BIOLOGICAL ACTIONS;92
8.9.9;References;92
8.10;10: Systemins;95
8.10.1;ABSTRACT;95
8.10.2;DISCOVERY OF SYSTEMINS;95
8.10.3;STRUCTURES OF SYSTEMINS AND OF THEIR PRECURSOR cDNAs;96
8.10.4;DISTRIBUTION OF SYSTEMIN SUBFAMILY mRNAs;97
8.10.5;PROCESSING OF THE SYSTEMIN FAMILY PRECURSOR PROTEINS;97
8.10.6;THE LeSys RECEPTOR;98
8.10.7;SOLUTION CONFORMATIONS OF SYSTEMIN SUBFAMILY MEMBERS;98
8.10.8;BIOLOGICAL ACTIONS OF SYSTEMIN FAMILY MEMBERS;98
8.10.9;Acknowledgments;99
8.10.10;References;99
9;II: Bacterial/Antibiotic Peptides Section;101
9.1;11: Cationic Antimicrobial Peptides—The Defensins;101
9.1.1;ABSTRACT;101
9.1.2;DISCOVERY;101
9.1.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;101
9.1.4;DISTRIBUTION AND EXPRESSION OF THE mRNA;102
9.1.5;PROCESSING;104
9.1.6;RECEPTORS;104
9.1.7;ACTIVE CONFORMATION;105
9.1.8;BIOLOGICAL ACTIONS;105
9.1.9;Acknowledgments;111
9.1.10;References;111
9.2;12: Cathelicidins: Cationic Host Defense and Antimicrobial Peptides;113
9.2.1;ABSTRACT;113
9.2.2;DISCOVERY;113
9.2.3;STRUCTURE OF THE PRECURSOR mRNA/STRUCTURAL GENE;113
9.2.4;DISTRIBUTION OF CATHELICIDINS;114
9.2.5;PROCESSING;114
9.2.6;RECEPTORS;115
9.2.7;ACTIVE AND/OR SOLUTION CONFORMATION;116
9.2.8;BIOLOGICAL FUNCTIONS;117
9.2.9;Acknowledgments;118
9.2.10;References;118
9.3;13: Microcins;121
9.3.1;ABSTRACT;121
9.3.2;DISCOVERY;121
9.3.3;STRUCTURE OF THE PRECURSOR mRNA/STRUCTURAL GENE;121
9.3.4;DISTRIBUTION OF THE mRNA;122
9.3.5;PROCESSING;122
9.3.6;RECEPTORS;124
9.3.7;ACTIVE AND/OR SOLUTION CONFORMATION;124
9.3.8;BIOLOGICAL ACTIONS;125
9.3.9;Acknowledgments;125
9.3.10;References;125
9.4;14: Peptaibols;129
9.4.1;ABSTRACT;129
9.4.2;INTRODUCTION;129
9.4.3;CHARACTERISTIC FEATURES OF THE PEPTAIBOLS;129
9.4.4;BIOLOGICAL ORIGINS AND BIOSYNTHESIS OF PEPTAIBOLS;131
9.4.5;PEPTAIBOL STRUCTURES;131
9.4.6;FUNCTIONS AND ACTIVITIES OF PEPTAIBOLS;132
9.4.7;Acknowledgments;133
9.4.8;References;133
9.5;15: Nonribosomally Synthesized Microbial Macrocyclic Peptides;135
9.5.1;ABSTRACT;135
9.5.2;STRUCTURAL DIVERSITY OF NRPS SYNTHESIZED PEPTIDES;135
9.5.3;MODULAR STRUCTURE OF NRPSs;136
9.5.4;MACROCYCLIZATION;138
9.5.5;STRUCTURE OF THE SURFACTIN THIOESTERASE DOMAIN;138
9.5.6;BIOCHEMICAL CHARACTERIZATION OF EXCISED THIOESTERASE DOMAINS;139
9.5.7;CHEMOENZYMATIC APPROACHES TOWARD NOVEL CYCLOPEPTIDES;140
9.5.8;THE COMBINATORIAL POTENTIAL OF TE DOMAINS TO SYNTHESIZE CYCLIC PEPTIDE LIBRARIES;141
9.5.9;Acknowledgments;141
9.5.10;References;141
9.6;16: Lantibiotics;143
9.6.1;ABSTRACT;143
9.6.2;DISCOVERY;143
9.6.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;143
9.6.4;DISTRIBUTION OF THE mRNA;143
9.6.5;PROCESSING;144
9.6.6;RECEPTORS;144
9.6.7;ACTIVE AND/OR SOLUTION CONFORMATION;144
9.6.8;BIOLOGICAL ACTIONS;146
9.6.9;Acknowledgments;149
9.6.10;References;149
9.7;17: The Nonlantibiotic Heat-Stable Bacteriocins in Gram-Positive Bacteria;153
9.7.1;ABSTRACT;153
9.7.2;DISCOVERY;153
9.7.3;SYNTHESIS;153
9.7.4;BIOLOGICAL ACTIONS AND RECEPTORS;156
9.7.5;STRUCTURE;157
9.7.6;FUTURE TRENDS;158
9.7.7;Acknowledgments;158
9.7.8;References;158
9.8;18: Colicins: Bacterial/Antibiotic Peptides;161
9.8.1;ABSTRACT;161
9.8.2;DISCOVERY AND CLASSIFICATION;161
9.8.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;161
9.8.4;THE DOMAIN CONCEPT;162
9.8.5;SEQUENCE COMPARISONS;163
9.8.6;X-RAY STRUCTURES OF COLICINS;166
9.8.7;MECHANISM OF IMPORT ACROSS OUTER MEMBRANE;168
9.8.8;AREAS OF RESEARCH ENCOMPASSED BY COLICIN STUDIES;168
9.8.9;Acknowledgment;168
9.8.10;References;168
10;III: Fungal/Antifungal Peptides Section;171
10.1;19: Fungal Peptides with Antifungal Activity;171
10.1.1;ABSTRACT;171
10.1.2;DISCOVERY;171
10.1.3;STRUCTURE;173
10.1.4;BIOLOGICAL ACTION;174
10.1.5;References;174
10.2;20: Toxins from Basidiomycete Fungi (Mushroom): Amatoxins, Phallotoxins, and Virotoxins;177
10.2.1;ABSTRACT;177
10.2.2;INTRODUCTION;177
10.2.3;DISCOVERY OF MUSHROOM TOXINS;177
10.2.4;STRUCTURES OF MUSHROOM TOXINS;179
10.2.5;TOXIC ACTIONS OF MUSHROOM TOXINS;179
10.2.6;Acknowledgments;181
10.2.7;References;181
10.3;21: Fungal Peptides with Ribonuclease Activity;183
10.3.1;ABSTRACT;183
10.3.2;DISCOVERY;183
10.3.3;STRUCTURE;183
10.3.4;BIOLOGICAL ACTION;185
10.3.5;References;189
10.4;22: Fungal Ribosome Inactivating Proteins;191
10.4.1;ABSTRACT;191
10.4.2;DISCOVERY;191
10.4.3;STRUCTURE;192
10.4.4;BIOLOGICAL ACTIONS;192
10.4.5;Acknowledgments;194
10.4.6;References;194
10.5;23: Peptides and Depsipeptides from Plant Pathogenic Fungi;197
10.5.1;ABSTRACT;197
10.5.2;PHYTOTOXINS;197
10.5.3;DEPSIPEPTIDES AND PEPTIDES;198
10.5.4;CONCLUSION;201
10.5.5;References;202
11;IV: Invertebrate Peptides Section;203
11.1;24: Insect Diuretic and Antidiuretic Hormones;203
11.1.1;ABSTRACT;203
11.1.2;DISCOVERY;203
11.1.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;204
11.1.4;DISTRIBUTION OF mRNA AND PEPTIDES;205
11.1.5;PEPTIDE PROCESSING;205
11.1.6;RECEPTORS;205
11.1.7;STRUCTURE-ACTIVITY AND ACTIVE CONFORMATION;206
11.1.8;BIOLOGICAL ACTIONS;206
11.1.9;CONCLUSION;207
11.1.10;References;207
11.2;25: Developmental Peptides: ETH, Corazonin, and PTTH;209
11.2.1;ABSTRACT;209
11.2.2;DISCOVERY;209
11.2.3;STRUCTURE OF THE PRECURSOR mRNA/GENE AND PEPTIDE PROCESSING;210
11.2.4;PTTH;211
11.2.5;DISTRIBUTION OF THE mRNA AND PEPTIDES;212
11.2.6;PTTH;212
11.2.7;RECEPTORS;212
11.2.8;ACTIVE AND/OR SOLUTION CONFORMATION;213
11.2.9;BIOLOGICAL ACTIONS;213
11.2.10;PTTH;214
11.2.11;References;214
11.3;26: Tachykinins and Tachykinin-Related Peptides in Invertebrates;217
11.3.1;ABSTRACT;217
11.3.2;DISCOVERY;217
11.3.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;218
11.3.4;DISTRIBUTION OF mRNA AND PEPTIDES;219
11.3.5;PEPTIDE PROCESSING;220
11.3.6;RECEPTORS OF TKRPs;220
11.3.7;STRUCTURE-ACTIVITY AND ACTIVE CONFORMATION;221
11.3.8;BIOLOGICAL ACTIONS;221
11.3.9;CONCLUSION;221
11.3.10;References;222
11.4;27: Proctolin in Insects;223
11.4.1;ABSTRACT;223
11.4.2;DISCOVERY;223
11.4.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;223
11.4.4;DISTRIBUTION OF mRNA;223
11.4.5;PROCESSING;224
11.4.6;RECEPTORS;225
11.4.7;STRUCTURE—ACTIVITY AND ACTIVE CONFORMATION;225
11.4.8;BIOLOGICAL ACTIONS;226
11.4.9;References;227
11.5;28: Sulfakinins;229
11.5.1;ABSTRACT;229
11.5.2;DISCOVERY;229
11.5.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;229
11.5.4;PROCESSING;230
11.5.5;TISSUE DISTRIBUTION;230
11.5.6;RECEPTORS;231
11.5.7;STRUCTURE/CONFORMATION-ACTIVITY RELATIONSHIPS;231
11.5.8;BIOLOGICAL ACTIONS;232
11.5.9;References;232
11.6;29: The Invertebrate AKH/RPCH Family;235
11.6.1;ABSTRACT;235
11.6.2;DISCOVERY;235
11.6.3;PEPTIDE AND PRECURSOR STRUCTURE AND PROCESSING;235
11.6.4;DISTRIBUTION;236
11.6.5;SOLUTION CONFORMATION OF AKH AND RECEPTORS FOR AKH;236
11.6.6;BIOLOGICAL ACTIONS;237
11.6.7;Acknowledgments;238
11.6.8;References;238
11.7;30: Insect Myosuppressins/FMRFamides and FL/IRFamides/NPFs;239
11.7.1;ABSTRACT;239
11.7.2;DISCOVERY;239
11.7.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;240
11.7.4;DISTRIBUTION OF mRNA;241
11.7.5;PROCESSING;242
11.7.6;RECEPTORS;242
11.7.7;STRUCTURE–ACTIVITY AND ACTIVE CONFORMATION;243
11.7.8;BIOLOGICAL ACTION;244
11.7.9;References;245
11.8;31: Allatostatins in the Insects;247
11.8.1;ABSTRACT;247
11.8.2;DISCOVERY;247
11.8.3;STRUCTURE OF ALLATOSTATIN PRECURSORS;247
11.8.4;DISTRIBUTION OF mRNA AND PEPTIDES;248
11.8.5;PEPTIDE PROCESSING;249
11.8.6;ALLATOSTATIN RECEPTORS;249
11.8.7;STRUCTURE–ACTIVITY AND ACTIVE CONFORMATIONS;250
11.8.8;BIOLOGICAL ACTIONS;251
11.8.9;CONCLUSION;251
11.8.10;References;251
11.9;32: The FXPRLamide (Pyrokinin/PBAN) Peptide Family;253
11.9.1;ABSTRACT;253
11.9.2;DISCOVERY;253
11.9.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;253
11.9.4;DISTRIBUTION OF mRNA AND PEPTIDES;254
11.9.5;PEPTIDE PROCESSING;255
11.9.6;RECEPTORS OF IXPRLamides;256
11.9.7;STRUCTURE–ACTIVITY RELATIONSHIPS AND ACTIVE CONFORMATION;256
11.9.8;BIOLOGICAL ACTIONS;257
11.9.9;References;257
11.10;33: Insect Pigment Dispersing Factor and Bursicon;259
11.10.1;ABSTRACT;259
11.10.2;INSECT PIGMENT DISPERSING FACTOR;259
11.10.3;BURSICON;261
11.10.4;References;265
11.11;34: Crustacean Bioactive Peptides;267
11.11.1;ABSTRACT;267
11.11.2;INTRODUCTION;267
11.11.3;PROCTOLIN;267
11.11.4;CRUSTACEAN CARDIOACTIVE PEPTIDE;267
11.11.5;SULFAKININS;270
11.11.6;NEUROPEPTIDE F;270
11.11.7;OPIOID–ENKEPHALIN;270
11.11.8;ORCOKININ AND ORCOMYOTROPIN;271
11.11.9;ALLATOSTATIN;271
11.11.10;TACHYKININ-RELATED PEPTIDES;272
11.11.11;KININS;272
11.11.12;PYROKININ/PBAN;272
11.11.13;SIFAMIDE;272
11.11.14;MISCELLANEOUS;273
11.11.15;References;273
11.12;35: Crustacean Chromatophorotrophins and Hyperglycemic Hormone Peptide Families;275
11.12.1;ABSTRACT;275
11.12.2;INTRODUCTION;275
11.12.3;CHROMATOPHOROTROPHIC HORMONES;275
11.12.4;CRUSTACEAN HYPERGLYCEMIC HORMONES;276
11.12.5;References;279
11.13;36: Molluscan Bioactive Peptides;281
11.13.1;ABSTRACT;281
11.13.2;FMRFamide, FMRFamide-RELATED PEPTIDES (FaRPs);281
11.13.3;PEPTIDES AND METABOLISM: ENERGY FLOW AND GROWTH;282
11.13.4;PEPTIDES AND FEEDING BEHAVIOR;283
11.13.5;PEPTIDES AND RENAL FUNCTION;284
11.13.6;TACHYKININS;284
11.13.7;References;285
11.14;37: Molluscan Peptides and Reproduction;287
11.14.1;ABSTRACT;287
11.14.2;PEPTIDES AND REPRODUCTION;287
11.14.3;DISCOVERY;289
11.14.4;VP/OT: DISCOVERY;289
11.14.5;PHEROMONES: DISCOVERY;290
11.14.6;References;291
11.15;38: Free-Living Nematode Peptides;293
11.15.1;ABSTRACT;293
11.15.2;INTRODUCTION;293
11.15.3;FMRFamide-LIKE PEPTIDES (FLPs);293
11.15.4;NEUROPEPTIDE-LIKE PEPTIDES (NLPs);296
11.15.5;INSULINS (INSs);296
11.15.6;ANTIMICROBIAL PEPTIDES;298
11.15.7;Acknowledgment;299
11.15.8;References;299
11.16;39: Parasitic Nematode Peptides;301
11.16.1;ABSTRACT;301
11.16.2;INTRODUCTION;301
11.16.3;FMRFamide-LIKE PEPTIDES (FLPs);301
11.16.4;TKQELE;305
11.16.5;References;305
12;V: Amphibian Peptides Section;307
12.1;40: Amphibian Tachykinins;307
12.1.1;ABSTRACT;307
12.1.2;DISCOVERY;307
12.1.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;308
12.1.4;AMPHIBIAN TK DISTRIBUTION;309
12.1.5;RECEPTORS;310
12.1.6;ACTIVE AND/OR SOLUTION CONFORMATION;310
12.1.7;BIOLOGICAL ACTIONS;310
12.1.8;PATHOLOGICAL IMPLICATIONS;313
12.1.9;References;313
12.2;41: Opioid Peptides from Frog Skin and Bv8-Related Peptides;315
12.2.1;ABSTRACT;315
12.2.2;OPIOID PEPTIDES;315
12.2.3;A BRIEF HISTORY;315
12.2.4;STRUCTURE AND CONFORMATION;316
12.2.5;BIOLOGICAL ACTIONS;317
12.2.6;Bv8/PROKINETICIN FAMILY (SWISS-PROT: Q9PW66);318
12.2.7;References;320
12.3;42: Amphibian Bombesin-like Peptides;323
12.3.1;ABSTRACT;323
12.3.2;INTRODUCTION;323
12.3.3;AMPHIBIAN BOMBESINS;323
12.3.4;AMPHIBIAN PHYLLOLITORINS;325
12.3.5;RANATENSIN-LIKE PEPTIDES;325
12.3.6;GASTRIN-RELEASING PEPTIDE;326
12.3.7;PHYLOGENETIC CONSIDERATIONS AND IMPLICATIONS FOR ADDITIONAL MAMMALIAN BOMBESIN-LIKE PEPTIDES;326
12.3.8;References;327
12.4;43: Host Defense Peptides from Australian Amphibians: Caerulein and Other Neuropeptides;329
12.4.1;ABSTRACT;329
12.4.2;INTRODUCTION;329
12.4.3;THE CAERULEIN PEPTIDES;329
12.4.4;PEPTIDES RELATED TO CAERULEIN;331
12.4.5;TRYPTOPHYLLIN PEPTIDES;332
12.4.6;DISULFIDE NEUROPEPTIDES FROM THE GENUS CRINIA;333
12.4.7;Acknowledgments;333
12.4.8;References;333
12.5;44: Bradykinin-Related Peptides from Frog Skin;337
12.5.1;ABSTRACT;337
12.5.2;DISCOVERY AND DISTRIBUTION;337
12.5.3;BIOSYNTHESIS OF BRADYKININ AND RELATED PEPTIDES;337
12.5.4;MOLECULAR VARIANTS OF BK;338
12.5.5;BIOLOGICAL ACTIVITIES;339
12.5.6;References;340
12.6;45: The Dermaseptins;341
12.6.1;ABSTRACT;341
12.6.2;THE DERMASEPTIN SUPERFAMILY;341
12.6.3;THE PREPRODERMASEPTINS;343
12.6.4;ACTIVITIES OF THE PREPRODERMASEPTINDERIVED PEPTIDES;346
12.6.5;STRUCTURAL FEATURES AND MECHANISMS OF MICROBICIDAL ACTIVITY;347
12.6.6;References;349
12.7;46: The Temporins;351
12.7.1;ABSTRACT;351
12.7.2;DISCOVERY;351
12.7.3;BIOSYNTHESIS OF THE TEMPORINS;352
12.7.4;MOLECULAR HETEROGENEITY OF THE TEMPORINS;353
12.7.5;BIOLOGICAL ACTIVITIES OF THE TEMPORINS;353
12.7.6;POTENTIAL CLINICAL AND COMMERCIAL APPLICATIONS;354
12.7.7;References;354
12.8;47: Chromogranins/Secretogranins and Derived Peptides: Insights from the Amphibian Model;357
12.8.1;ABSTRACT;357
12.8.2;DISCOVERY;357
12.8.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;357
12.8.4;DISTRIBUTION OF THE mRNA;360
12.8.5;BIOLOGICAL ACTIONS;362
12.8.6;Acknowledgments;364
12.8.7;References;364
12.9;48: Sodefrin and Related Pheromones;367
12.9.1;ABSTRACT;367
12.9.2;DISCOVERY;367
12.9.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;368
12.9.4;DISTRIBUTION OF THE mRNA;369
12.9.5;PROCESSING OF THE PRECURSORS;369
12.9.6;RECEPTORS;369
12.9.7;STRUCTURE–ACTIVITY RELATIONSHIPS;371
12.9.8;BIOLOGICAL ACTIONS;371
12.9.9;PHYSIOLOGICAL IMPLICATION;372
12.9.10;References;372
12.10;49: Amphibian Neurohypophysial Peptides;373
12.10.1;ABSTRACT;373
12.10.2;DISCOVERY;373
12.10.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;373
12.10.4;DISTRIBUTION OF AVT AND MT;374
12.10.5;RECEPTOR STRUCTURE AND DISTRIBUTION;374
12.10.6;MAJOR BIOLOGICAL ACTIONS OF AVT AND MT;374
12.10.7;STRUCTURE AND FUNCTION OF HYDRINS;375
12.10.8;References;376
12.11;50: Bombinins;379
12.11.1;ABSTRACT;379
12.11.2;DISCOVERY;379
12.11.3;SOLUTION CONFORMATION;381
12.11.4;STRUCTURE OF THE PRECURSOR mRNA/GENE;381
12.11.5;BIOLOGICAL ACTIVITY;381
12.11.6;MODE OF ACTION STUDIES;382
12.11.7;Acknowledgments;383
12.11.8;References;383
13;VI: Venom Peptides Section;385
13.1;51: Scorpion Venom Peptides;385
13.1.1;INTRODUCTION;385
13.1.2;DISCOVERY AND DOCUMENTED BIODIVERSITY;385
13.1.3;THREE-DIMENSIONAL FOLDING;386
13.1.4;SCORPION TOXIN PRECURSORS;387
13.1.5;RECEPTOR SITES;387
13.1.6;MOLECULAR BASIS OF THEIR ACTIVITY;387
13.1.7;CONCLUSION;389
13.1.8;Acknowledgments;389
13.1.9;References;389
13.2;52: Snake Venom Peptides;401
13.2.1;ABSTRACT;401
13.2.2;INTRODUCTION;401
13.2.3;THREE-FINGER TOXINS;401
13.2.4;PROTEASE INHIBITOR HOMOLOGS;404
13.2.5;CROTAMINE-LIKE MYOTOXINS;405
13.2.6;SARAFOTOXINS;405
13.2.7;CRISP FAMILY TOXINS;405
13.2.8;NATRIURETIC PEPTIDES;405
13.2.9;DISINTEGRINS;406
13.2.10;C-TYPE LECTINS AND LECTIN-LIKE PROTEINS;406
13.2.11;WAGLERINS;406
13.2.12;BRADYKININ-POTENTIATING PEPTIDES;406
13.2.13;AVIT PEPTIDES;407
13.2.14;MISCELLANEOUS PEPTIDES;407
13.2.15;References;408
13.3;53: Sea Anemone Venom Peptides;409
13.3.1;ABSTRACT;409
13.3.2;INTRODUCTION;409
13.3.3;ION CHANNEL BLOCKERS AND MODULATORS;409
13.3.4;CYTOLYSINS;411
13.3.5;OTHER BIOACTIVE PEPTIDES;412
13.3.6;Acknowledgments;412
13.3.7;References;412
13.4;54: Spider Venom Peptides;415
13.4.1;ABSTRACT;415
13.4.2;INTRODUCTION;415
13.4.3;METHODOLOGICAL APPROACHES IN THE ISOLATION OF NOVEL SPIDER VENOM PEPTIDES;415
13.4.4;STRUCTURE OF THE PRECURSOR SPIDER VENOM PEPTIDE AND POSTTRANSLATIONAL PROCESSING;416
13.4.5;STRUCTURAL ORGANIZATION OF SPIDER VENOM PEPTIDES: VARIATIONS ON AN ANCESTRAL FOLD;416
13.4.6;SPIDER PEPTIDE TOXINS MODULATING Nav CHANNEL FUNCTION: BLOCKERS AND GATING MODIFIERS;416
13.4.7;SPIDER PEPTIDE TOXINS MODULATING VOLTAGE-GATED POTASSIUM CHANNELS;420
13.4.8;SPIDER PEPTIDE TOXINS MODULATING ON Cav CHANNELS;421
13.4.9;SPIDER PEPTIDE TOXINS ACTING ON ACID-SENSING ION CHANNELS;422
13.4.10;SPIDER PEPTIDE TOXINS WITH NONSELECTIVE ACTIONS ON VOLTAGE-GATED ION CHANNELS: PROMISCUOUS TOXINS;422
13.4.11;SPIDER PEPTIDE TOXINS ACTING ON MECHANOSENSITIVE ION CHANNELS;422
13.4.12;SPIDER TOXINS ACTING ON GLUTAMATE RECEPTORS OR TRANSPORTERS;422
13.4.13;SPIDER TOXINS ACTING ON NEUROTRANSMITTER RELEASE (PRESYNAPTIC TOXINS);423
13.4.14;SPHINGOMYELINASES D TOXINS FROM SPIDER VENOMS;423
13.4.15;ANTIMICROBIAL AND CYTOLYTIC PEPTIDE TOXINS FROM SPIDER VENOM;424
13.4.16;CONCLUSION;425
13.4.17;References;425
13.5;55: Conus Snail Venom Peptides;427
13.5.1;ABSTRACT;427
13.5.2;INTRODUCTION: THE BIODIVERSITY OF VENOMOUS MOLLUSCS;427
13.5.3;DISCOVERY OF CONOTOXINS;427
13.5.4;PRECURSOR STRUCTURE, EXPRESSION, AND PROCESSING: CONOTOXIN SUPERFAMILIES;428
13.5.5;DEFINITION OF CONOTOXIN FAMILIES, RECEPTOR TARGETS, STRUCTURES;430
13.5.6;BIOLOGICAL MECHANISMS, THERAPEUTIC APPLICATIONS;432
13.5.7;Acknowledgments;433
13.5.8;References;433
13.6;56: Insect Venom Peptides;435
13.6.1;ABSTRACT;435
13.6.2;INTRODUCTION;435
13.6.3;PEPTIDES FROM THE VENOMS OF SOCIAL HYMENOPTERA;436
13.6.4;PEPTIDE TOXINS FROM SOCIAL WASPS;437
13.6.5;PEPTIDES FROM THE VENOMS OF SOLITARY WASPS;438
13.6.6;PEPTIDES FROM ANT VENOMS;439
13.6.7;Aknowledgments;440
13.6.8;References;440
13.7;57: Worm Venom Peptides;443
13.7.1;ABSTRACT;443
13.7.2;INTRODUCTION;443
13.7.3;NEMERTINE PEPTIDE NEUROTOXINS;444
13.7.4;NEMERTINE PEPTIDE CYTOLYSINS;445
13.7.5;ANNELID (GLYCERA) NEUROTOXIN;445
13.7.6;PEPTIDE CYTOLYSINS FROM OTHER WORM PHYLA;446
13.7.7;CONCLUSION;446
13.7.8;References;446
13.8;58: Targets and Therapeutic Properties of Venom Peptides;449
13.8.1;ABSTRACT;449
13.8.2;ANTICOAGULANTS AND THROMBOLYTIC AGENTS;449
13.8.3;ANTIHYPERTENSIVE AGENTS;456
13.8.4;ANTIARRHYTHMIC AGENTS;456
13.8.5;CONGESTIVE HEART FAILURE;456
13.8.6;ANTIMICROBIAL PEPTIDES;456
13.8.7;IMMUNOMODULATORY PEPTIDES;457
13.8.8;ANTITUMOR PEPTIDES;457
13.8.9;ANALGESIA;458
13.8.10;DIABETES MELLITUS;458
13.8.11;Acknowledgments;458
13.8.12;References;458
13.9;59: Structure-Function Strategies to Improve the Pharmacological Value of Animal Toxins;461
13.9.1;ABSTRACT;461
13.9.2;CHEMICAL SYNTHESIS VERSUS GENETIC ENGINEERING;461
13.9.3;PEPTIDE IMPROVEMENT;461
13.9.4;DESIGN OF NOVEL PEPTIDE ANALOGS;462
13.9.5;BENEFITS OF SIZE REDUCTION IN PEPTIDES;462
13.9.6;RELEVANCE OF CHIMERA AND LABELING APPROACHES;462
13.9.7;STRATEGIES IMPLYING A CHANGE IN THE PATTERN OF HALF-CYSTINE PAIRS;463
13.9.8;WHAT ABOUT THE DIPOLE MOMENT OF VENOM PEPTIDES?;464
13.9.9;FUNCTIONAL DERIVATION OF VENOM PEPTIDES;464
13.9.10;IMPROVING PEPTIDE STABILITY;464
13.9.11;CONCLUSION;465
13.9.12;References;465
14;VII: Cancer/Anticancer Peptides Section;467
14.1;60: Analogs of Luteinizing Hormone-Releasing Hormone (LHRH) in Cancer;467
14.1.1;ABSTRACT;467
14.1.2;INTRODUCTION;467
14.1.3;ANTAGONISTS OF LHRH;468
14.1.4;RECEPTORS FOR LHRH ON TUMORS;468
14.1.5;CYTOTOXIC LHRH ANALOGS;469
14.1.6;EFFECTS OF ANALOGS OF LHRH ON TUMORS;469
14.1.7;CYTOTOXIC ANALOGS OF LHRH;469
14.1.8;SIDE EFFECTS OF CYTOTOXIC LHRH ANALOGS;471
14.1.9;CONCLUSION;472
14.1.10;References;472
14.2;61: Bombesin-Related Peptides and Neurotensin: Effects on Cancer Growth/Proliferation and Cellular Signaling in Cancer;475
14.2.1;ABSTRACT;475
14.2.2;INTRODUCTION;475
14.2.3;BN-RELATED PEPTIDES (GRP, NMB);475
14.2.4;NEUROTENSIN (NT);477
14.2.5;References;478
14.3;62: Somatostatin and NPY;481
14.3.1;ABSTRACT;481
14.3.2;INTRODUCTION;481
14.3.3;SOMATOSTATIN;481
14.3.4;NPY;484
14.3.5;References;486
14.4;63: Bradykinin and Cancer;489
14.4.1;ABSTRACT;489
14.4.2;INTRODUCTION;489
14.4.3;KININ CHEMISTRY AND BIOLOGY;489
14.4.4;BRADYKININ ANTAGONISTS;490
14.4.5;BRADYKININ AND CANCER;491
14.4.6;References;492
14.5;64: Endothelin;493
14.5.1;ABSTRACT;493
14.5.2;ENDOTHELIN-1;493
14.5.3;ET-1 ASSOCIATED SIGNAL TRANSDUCTION PATHWAYS;493
14.5.4;ENDOTHELIN EXPRESSION IN CANCER;493
14.5.5;ENDOTHELIN RECEPTOR EXPRESSION IN CANCER;494
14.5.6;ENDOTHELIN AS A MITOGEN;495
14.5.7;ENDOTHELIN AND APOPTOSIS;495
14.5.8;ENDOTHELIN AND ANGIOGENESIS;495
14.5.9;ENDOTHELIN-1 AND TUMOR PROGRESSION/METASTASES;496
14.5.10;ENDOTHELIN ANTAGONISM IN VIVO;496
14.5.11;CLINICAL TRIALS;496
14.5.12;References;496
14.6;65: Adrenomedullin: An Esoteric Juggernaut of Human Cancers;499
14.6.1;ABSTRACT;499
14.6.2;INTRODUCTION;499
14.6.3;AM EXPRESSION;499
14.6.4;GROWTH REGULATION;500
14.6.5;ANTIAPOPTOSIS;500
14.6.6;MIGRATION/INVASION;501
14.6.7;ANGIOGENESIS;501
14.6.8;IMMUNE REGULATION;501
14.6.9;THERAPEUTIC STRATEGIES AND CONCLUSION;502
14.6.10;References;502
14.7;66: Angiotensin Peptides and Cancer;505
14.7.1;ABSTRACT;505
14.7.2;INTRODUCTION;505
14.7.3;ACE AND AT1 RECEPTOR POLYMORPHISMS AND CANCER;506
14.7.4;EFFECTS OF ACE INHIBITORS AND ARBs ON CANCER CELL GROWTH AND TUMORIGENESIS;506
14.7.5;MECHANISMS OF ACTION OF ANG II;507
14.7.6;INHIBITION OF HUMAN CANCER CELL GROWTH BY ANG-(1-7);508
14.7.7;CONCLUSION;509
14.7.8;References;509
14.8;67: Gastrin and Cancer;513
14.8.1;ABSTRACT;513
14.8.2;INTRODUCTION;513
14.8.3;EXPRESSION OF GASTRINS IN NORMAL TISSUE;513
14.8.4;THE GASTRIN RECEPTOR(S);514
14.8.5;EXPRESSION OF GASTRIN IN TUMORS;514
14.8.6;GASTRIN AS A TUMOR GROWTH FACTOR;515
14.8.7;CONCLUSION;515
14.8.8;References;516
14.9;68: VIP and PACAP as Autocrine Growth Factors in Breast and Lung Cancer;519
14.9.1;ABSTRACT;519
14.9.2;INTRODUCTION;519
14.9.3;VIP/PACAP PEPTIDES;519
14.9.4;VIP RECEPTORS;520
14.9.5;SECOND MESSENGERS;520
14.9.6;PROLIFERATION;521
14.9.7;TUMOR IMAGING;521
14.9.8;CONCLUSION;521
14.9.9;References;522
14.10;69: Oxytocin and Cancer;525
14.10.1;ABSTRACT;525
14.10.2;MOVING FROM PHYSIOLOGY TO NEOPLASTIC PATHOLOGY;525
14.10.3;OT AS A MODULATOR OF CELL GROWTH IN OTR-EXPRESSING TUMORS;526
14.10.4;THE OT/OTR SYSTEM AND CANCER;527
14.10.5;References;527
14.11;70: Antagonists of Growth Hormone–Releasing Hormone (GHRH) in Cancer;529
14.11.1;ABSTRACT;529
14.11.2;INTRODUCTION;529
14.11.3;THERAPEUTIC INDICATIONS OF GHRH ANTAGONISTS;530
14.11.4;ANTAGONISTIC ANALOGS OF GHRH;530
14.11.5;GHRH AND GHRH RECEPTORS IN HUMAN CANCERS;531
14.11.6;MECHANISMS OF TUMOR INHIBITION BY GHRH ANTAGONISTS;532
14.11.7;INHIBITORY EFFECTS OF GHRH ANTAGONISTS ON HUMAN EXPERIMENTAL CANCERS IN VIVO;532
14.11.8;CONCLUSION;533
14.11.9;References;534
15;VIII: Vaccine Peptides Section;537
15.1;71: Cancer Immunotherapy with Rationally Designed Synthetic Peptides;537
15.1.1;ABSTRACT;537
15.1.2;CANCER IMMUNOTHERAPY;537
15.1.3;CURRENT VACCINATION STRATEGIES;538
15.1.4;ACTIVE IMMUNOTHERAPEUTIC STRATEGIES USING PEPTIDES;539
15.1.5;IDENTIFICATION OF T AND B CELL EPITOPES;540
15.1.6;RATIONAL DESIGN OF PEPTIDE VACCINES;541
15.1.7;ANTITUMOR IMMUNITY WITH PEPTIDE VACCINES;542
15.1.8;CONCLUSION;542
15.1.9;References;543
15.2;72: Peptide Vaccines for Cancer Treatment;545
15.2.1;ABSTRACT;545
15.2.2;USING THE IMMUNE SYSTEM TO TREAT CANCER;545
15.2.3;IDENTIFICATION OF TUMOR ANTIGENS AND PEPTIDES USING ENDOGENOUS IMMUNITY PRESENT IN CANCER PATIENTS;546
15.2.4;COMMON TUMOR ANTIGENS AND ANTIGENIC PEPTIDES RECOGNIZED BY T CELLS;546
15.2.5;FEATURES OF TUMOR-SPECIFIC T CELLS;548
15.2.6;CLINICAL TRIALS OF PEPTIDE BASED CANCER VACCINES;548
15.2.7;STRATEGIES FOR ENHANCING THE EFFICACY OF PEPTIDE-BASED VACCINES;549
15.2.8;CONCLUSION;550
15.2.9;Acknowledgments;550
15.2.10;References;550
15.3;73: Antiadhesin Synthetic Peptide Consensus Sequence Vaccine and Antibody Therapeutic for Pseudomonas Aeruginosa;553
15.3.1;ABSTRACT;553
15.3.2;DISEASE TARGET;553
15.3.3;BACKGROUND AND AVAILABLE THERAPIES;553
15.3.4;WHY PEPTIDES;554
15.3.5;CONTRIBUTIONS;556
15.3.6;FUTURE OUTLOOK;559
15.3.7;CONCLUSION;559
15.3.8;References;560
15.4;74: Peptide Vaccines for Malaria;561
15.4.1;ABSTRACT;561
15.4.2;INTRODUCTION;561
15.4.3;MALARIAL VACCINES;562
15.4.4;MAIN MALARIAL ANTIGENS INVOLVED IN TARGET CELL BINDING;563
15.4.5;VACCINE DESIGN BASED ON A STRUCTURAL-FUNCTION RELATIONSHIP;564
15.4.6;DESIGN BASED ON THE MHC-PEPTIDE-TCR COMPLEX CONFORMATION;566
15.4.7;DESIGN BASED ON STRUCTURALLY MODIFIED ANTIGEN BINDING TO HLADRb1* MOLECULES;567
15.4.8;DESIGN BASED ON MALARIAL ANTIGENS’ STRUCTURAL MODIFICATION BY INTRODUCING PEPTIDE BOND ISOSTERS;568
15.4.9;CONCLUSION;570
15.4.10;Acknowledgments;570
15.4.11;References;570
15.5;75: Peptide Vaccine for Otitis Media;573
15.5.1;ABSTRACT;573
15.5.2;DISEASE TARGET;573
15.5.3;BACKGROUND OF AVAILABLE THERAPIES;573
15.5.4;WHY PEPTIDES?;574
15.5.5;OUR CONTRIBUTIONS TO THE AREA;577
15.5.6;FUTURE OUTLOOK;578
15.5.7;References;578
15.6;76: Peptide Vaccine for Alzheimer’s Disease;581
15.6.1;ABSTRACT;581
15.6.2;INTRODUCTION;581
15.6.3;IN VITRO MODULATION OF b-AMYLOID FORMATION;581
15.6.4;EFRH PHAGE ELICITS ANTIBODIES AGAINST b-AMYLOID PEPTIDE;582
15.6.5;PEPTIDES AS VACCINES FOR PREVENTION AND/OR REDUCTION OF AMYLOID PLAQUES IN AD TRANSGENIC MICE;583
15.6.6;ACTIVE IMMUNIZATION OF hAPP TRANSGENIC MICE WITH EFRH-PHAGE AS PEPTIDE VACCINE;584
15.6.7;FUTURE OUTLOOK;585
15.6.8;Acknowledgments;585
15.6.9;References;585
15.7;77: Peptide Dendrimers as Immunogens;587
15.7.1;ABSTRACT;587
15.7.2;INTRODUCTION;587
15.7.3;BACKGROUND AND DISCOVERY;587
15.7.4;DESIGN OF PEPTIDE DENDRIMERS AS IMMUNOGENS;588
15.7.5;IMMUNOLOGICAL PROPERTY OF MAPs;589
15.7.6;CELL-MEDIATED RESPONSES INDUCED BY LIPIDATED MAPs;589
15.7.7;REASONS FOR INCREASED IMMUNOGENICITY;590
15.7.8;SYNTHESIS;590
15.7.9;CONTRIBUTION AND FUTURE OUTLOOK;591
15.7.10;References;592
16;IX: Immunological and Inflammatory Peptides Section;593
16.1;78: Chemotactic Peptide Ligands for Formylpeptide Receptors Influencing Inflammation;593
16.1.1;ABSTRACT;593
16.1.2;BACKGROUND;593
16.1.3;FORMYLPEPTIDE RECEPTORS;593
16.1.4;AGONIST PEPTIDES OF FPRs;594
16.1.5;MAMMALIAN PEPTIDES;595
16.1.6;PERSPECTIVES;597
16.1.7;Acknowledgments;597
16.1.8;References;597
16.2;79: Complement-Derived Inflammatory Peptides: Anaphylatoxins;599
16.2.1;ABSTRACT;599
16.2.2;HISTORICAL PERSPECTIVE AND SCOPE;599
16.2.3;PRECURSOR mRNA/GENE STRUCTURE, EXPRESSION, AND REGULATION OF ANAPHYLATOXINS;599
16.2.4;GENERATION OF C3a AND C5a ANAPHYLATOXINS;600
16.2.5;STRUCTURE OF ANAPHYLATOXINS;601
16.2.6;RECEPTORS FOR ANAPHYLATOXINS;602
16.2.7;BIOLOGICAL ACTIONS OF ANAPHYLATOXINS;602
16.2.8;PATHOPHYSIOLOGICAL IMPLICATIONS OF ANAPHYLATOXINS;603
16.2.9;Acknowledgment;603
16.2.10;References;603
16.3;80: Chemokines: A New Peptide Family of Neuromodulators;605
16.3.1;ABSTRACT;605
16.3.2;DISCOVERY;606
16.3.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;606
16.3.4;DISTRIBUTION OF SDF-1 mRNA AND PROTEIN;606
16.3.5;PROCESSING OF THE PRECURSOR;608
16.3.6;RECEPTORS AND SIGNALING CASCADES;608
16.3.7;RECEPTOR EXPRESSION AND DISTRIBUTION;608
16.3.8;CONFORMATION;609
16.3.9;BIOLOGICAL ACTIONS;609
16.3.10;PATHOPHYSIOLOGICAL IMPLICATIONS;610
16.3.11;References;610
16.4;81: Immune Peptides Related to Dipeptidyl Aminopeptidase IV/CD26;613
16.4.1;ABSTRACT;613
16.4.2;INTRODUCTION;613
16.4.3;DP IV/CD26 IN THE IMMUNE SYSTEM;613
16.4.4;DP IV EFFECTOR PEPTIDES;614
16.4.5;PRIMARY DP IV EFFECTOR PEPTIDES;615
16.4.6;SECONDARY IMMUNORELEVANT DP IV PEPTIDE SUBSTRATES;616
16.4.7;PEPTIDE INHIBITORS OF DP IV;617
16.4.8;References;617
16.5;82: RGD-Peptides and Some Immunological Problems;619
16.5.1;ABSTRACT;619
16.5.2;DISCOVERY OF THE ANTIADHESIVE RGD-PEPTIDES;619
16.5.3;RGD-PEPTIDES IN PLATELET AGGREGATION;620
16.5.4;BIOLOGICALLY ACTIVE CONFORMATION OF RGD-PEPTIDES;621
16.5.5;RGD PEPTIDES IN IMMUNOLOGICAL PHENOMENA;621
16.5.6;RGD-PEPTIDES AND PATHOGEN INVASIONS;622
16.5.7;RGD-PEPTIDES IN OTHER PATHOLOGICAL PHENOMENA;622
16.5.8;RGD RETROSEQUENCES IN PROTEINS;623
16.5.9;References;623
16.6;83: Neuropeptides That Regulate Immune Responses;625
16.6.1;ABSTRACT;625
16.6.2;Acknowledgment;628
16.6.3;References;628
16.7;84: Peptides as Targets of T Cell-Mediated Immune Responses;631
16.7.1;ABSTRACT;631
16.7.2;INTRODUCTION;631
16.7.3;MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I AND CLASS II MOLECULES;632
16.7.4;CHARACTERISTICS OF PEPTIDES PRESENTED BY MHC-CLASS I;633
16.7.5;CHARACTERISTICS OF PEPTIDES PRESENTED BY MHC-CLASS II;634
16.7.6;BIOLOGICAL ROLES OF MHC-BOUND PEPTIDES;635
16.7.7;AUTOIMMUNE DISEASES;636
16.7.8;THERAPEUTIC USE OF PEPTIDES;637
16.7.9;CONCLUSION;638
16.7.10;References;638
16.8;85: The Use of Positional Scanning Synthetic Peptide Combinatorial Libraries to Identify Immunological Relevant Peptides;641
16.8.1;ABSTRACT;641
16.8.2;DEFINITION OF POSITIONAL SCANNING SYNTHETIC COMBINATORIAL PEPTIDE LIBRARIES (PS-SCL);641
16.8.3;USE OF PS-SCL TO DETERMINE ANTIBODY LIGANDS;642
16.8.4;USE OF PS-SCL FOR T CELL EPITOPE MAPPING;644
16.8.5;USE OF PS-SCL TO IDENTIFY MHC BINDING MOTIFS;645
16.8.6;CONCLUSION;646
16.8.7;References;646
16.9;86: Copolymer 1 and Related Peptides as Immunomodulating Agents;649
16.9.1;ABSTRACT;649
16.9.2;INTRODUCTION;649
16.9.3;SUPPRESSION OF EAE BY GA;650
16.9.4;OTHER PEPTIDES RELATED TO MS;650
16.9.5;CLINICAL TRIALS WITH COPOLYMER 1;651
16.9.6;MECHANISM OF ACTION OF GLATIRAMER ACETATE;651
16.9.7;IN SITU IMMUNOMODULATION AND NEUROGENRATION IN THE CNS;652
16.9.8;POTENTIAL OF GA FOR THE SUPPRESSION OF OTHER AUTOIMMUNE DISORDERS—STUDIES ON INFLAMMATORY BOWEL DISEASES;653
16.9.9;EFFECT OF COPOLYMER 1 ON GRAFT REJECTION;653
16.9.10;CONCLUSION;654
16.9.11;References;654
16.10;87: CLIP—A Multifunctional MHC Class II–Associated Self-Peptide;657
16.10.1;ABSTRACT;657
16.10.2;INTRODUCTION;657
16.10.3;THE CLIP RECEPTORS: MHC CLASS II MOLECULES;657
16.10.4;PROTEOLYSIS OF II AND GENERATION OF CLIP;660
16.10.5;FLANKING RESIDUES AND SELF-RELEASE OF CLIP;661
16.10.6;A CHAPERONE FACILITATING CLIP RELEASE: HLA-DM/H2-DM;661
16.10.7;MEMBRANE MICRODOMAINS;662
16.10.8;CLIP AS AN ANTAGONIST OF TH1 POLARIZATION;663
16.10.9;CONCLUSION;664
16.10.10;References;665
17;X: Brain Peptides Section;667
17.1;88: Vasopressin and Oxytocin;667
17.1.1;ABSTRACT;667
17.1.2;DISCOVERY;667
17.1.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;668
17.1.4;DISTRIBUTION OF THE mRNA;669
17.1.5;PROCESSING OF THE PRECURSOR;670
17.1.6;RECEPTORS;671
17.1.7;ACTIVE AND/OR SOLUTION CONFORMATION;672
17.1.8;BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY;672
17.1.9;PATHOPHYSIOLOGICAL IMPLICATIONS;672
17.1.10;References;673
17.2;89: Thyrotrophin-Releasing Hormone: New Functions for an Ancient Peptide;675
17.2.1;ABSTRACT;675
17.2.2;DISCOVERY OF TRH;675
17.2.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;675
17.2.4;DISTRIBUTION OF PRE-PROTRH mRNA AND PRE-PRO-TRH-DERIVED PEPTIDES;676
17.2.5;PROCESSING OF THE TRH PRECURSOR;676
17.2.6;DISTRIBUTION OF TRH RECEPTORS AND THE TRH DEGRADING ENZYME;676
17.2.7;TRH RECEPTOR SIGNALING CASCADES;677
17.2.8;BIOLOGICAL ACTIONS OF TRH WITHIN THE BRAIN AND PITUITARY;677
17.2.9;PATHOPHYSIOLOGICAL IMPLICATIONS;679
17.2.10;References;679
17.3;90: Gonadotrophin Releasing Hormone;681
17.3.1;ABSTRACT;681
17.3.2;DISCOVERY AND BACKGROUND;681
17.3.3;STRUCTURE OF GnRHS AND THEIR PRECURSORS;681
17.3.4;GnRH DISTRIBUTION;683
17.3.5;PROCESSING OF THE GnRH PRECURSOR;684
17.3.6;GnRH RECEPTORS AND SIGNALLING CASCADES;684
17.3.7;PHYSICAL STRUCTURE OF GnRH;688
17.3.8;BIOLOGICAL ACTIONS;688
17.3.9;PATHOPHYSIOLOGY;689
17.3.10;References;690
17.4;91: Brain Somatostatin-Related Peptides;691
17.4.1;ABSTRACT;691
17.4.2;DISCOVERY;691
17.4.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;691
17.4.4;DISTRIBUTION OF THE mRNAs AND PEPTIDES;692
17.4.5;PROCESSING OF THE PRECURSORS AND DEGRADATION OF THE PEPTIDE;694
17.4.6;RECEPTORS AND SIGNALING CASCADES;694
17.4.7;INFORMATION ON ACTIVE AND/OR SOLUTION CONFORMATION;696
17.4.8;BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY;697
17.4.9;PATHOPHYSIOLOGICAL IMPLICATIONS;697
17.4.10;References;699
17.5;92: Corticotrophin-Releasing Hormone (CRH) Peptide Family;701
17.5.1;ABSTRACT;701
17.5.2;DISCOVERY;701
17.5.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;702
17.5.4;DISTRIBUTION AND EXPRESSION OF mRNA;704
17.5.5;PROCESSING OF PREPROHORMONE;704
17.5.6;RECEPTORS AND BINDING PROTEINS;706
17.5.7;BIOLOGICAL ACTIONS IN THE CENTRAL NERVOUS SYSTEM;706
17.5.8;PATHOPHYSIOLOGICAL IMPLICATIONS;707
17.5.9;References;707
17.6;93: Growth Hormone-Releasing Hormone;709
17.6.1;ABSTRACT;709
17.6.2;DISCOVERY OF GHRH;709
17.6.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;709
17.6.4;EXPRESSION OF GHRH IN THE BRAIN;710
17.6.5;PROCESSING OF GHRH PRECURSOR;711
17.6.6;GHRH RECEPTOR;711
17.6.7;GHRH SIGNALING;713
17.6.8;CONFORMATION OF GHRH AND SYNTHESIS OF ANALOGS;714
17.6.9;BIOLOGICAL ACTIVITY OF GHRH;714
17.6.10;PATHOPHYSIOLOGICAL IMPLICATIONS;715
17.6.11;References;715
17.7;94: PACAP/VIP;719
17.7.1;ABSTRACT;719
17.7.2;DISCOVERY;719
17.7.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;719
17.7.4;DISTRIBUTION OF THE mRNA;720
17.7.5;PROCESSING OF THE PRECURSOR;720
17.7.6;RECEPTORS AND SIGNALING CASCADES;722
17.7.7;SOLUTION STRUCTURE COMPARISON;723
17.7.8;BIOLOGICAL ACTIONS IN THE BRAIN AND THE PITUITARY;723
17.7.9;PATHOPHYSIOLOGY OF PACAP/VIP;725
17.7.10;References;726
17.8;95: Neuropeptide Y;729
17.8.1;ABSTRACT;729
17.8.2;DISCOVERY OF NPY AND HOMOLOGS;729
17.8.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;729
17.8.4;PROCESSING OF THE NPY PRECURSOR;731
17.8.5;DISTRIBUTION OF NPY mRNA AND PROTEIN;731
17.8.6;STRUCTURE OF NPY-LIKE PEPTIDES;732
17.8.7;RECEPTORS AND SIGNALING CASCADES;732
17.8.8;BIOLOGICAL ACTIONS;732
17.8.9;PATHOPHYSIOLOGICAL IMPLICATIONS;733
17.8.10;Acknowledgment;733
17.8.11;References;733
17.9;96: Melanocortins;735
17.9.1;ABSTRACT;735
17.9.2;DISCOVERY;735
17.9.3;STRUCTURE OF THE PROOPIOMELANOCORTIN mRNA/GENE;735
17.9.4;DISTRIBUTION OF POMC mRNA AND MELANOCORTINS IN THE BRAIN;736
17.9.5;PROCESSING OF PROOPIOMELANOCORTIN;737
17.9.6;CONTROL OF BIOSYNTHESIS AND RELEASE OF BRAIN MELANOCORTINS;738
17.9.7;MELANOCORTIN RECEPTOR FAMILY;738
17.9.8;STRUCTURE–ACTIVITY RELATIONSHIPS FOR MELANOCORTINS;738
17.9.9;BIOLOGICAL ACTIONS WITHIN THE BRAIN;739
17.9.10;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;741
17.9.11;References;741
17.10;97: Cocaine- and Amphetamine-Regulated Transcript (CART);743
17.10.1;ABSTRACT;743
17.10.2;DISCOVERY;743
17.10.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;743
17.10.4;PROCESSING OF CART PEPTIDES;743
17.10.5;DISTRIBUTION OF CART mRNA AND PEPTIDES;744
17.10.6;RECEPTORS AND SIGNALING CASCADES;745
17.10.7;BIOLOGICAL ACTIONS OF CART PEPTIDES WITHIN THE BRAIN AND PITUITARY;745
17.10.8;PHYSIOPATHOLOGICAL IMPLICATIONS;747
17.10.9;References;747
17.11;98: The Melanin-Concentrating Hormone;751
17.11.1;ABSTRACT;751
17.11.2;DISCOVERY;751
17.11.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;752
17.11.4;DISTRIBUTION OF THE mRNA/PEPTIDES;754
17.11.5;PROCESSING OF THE MCH PRECURSOR;755
17.11.6;RECEPTORS AND SIGNALING CASCADES;755
17.11.7;ACTIVE STRUCTURE OF THE MCH PEPTIDE AND RECEPTOR CONFORMATION;757
17.11.8;BIOLOGICAL ACTIONS OF PRO-MCH-DERIVED PEPTIDES;757
17.11.9;PATHOPHYSIOLOGICAL IMPLICATIONS;758
17.11.10;References;759
17.12;99: CCK/Gastrin;761
17.12.1;ABSTRACT;761
17.12.2;DISCOVERY;761
17.12.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;761
17.12.4;DISTRIBUTION OF CCK;761
17.12.5;PROCESSING OF THE PRECURSOR;762
17.12.6;RECEPTORS AND SIGNALING CASCADES;763
17.12.7;ACTIVE AND/OR SOLUTION CONFORMATION;764
17.12.8;BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY;764
17.12.9;PATHOPHYSIOLOGICAL IMPLICATIONS;765
17.12.10;References;765
17.13;100: The Hypocretins (Orexins);767
17.13.1;ABSTRACT;767
17.13.2;DISCOVERY;767
17.13.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;767
17.13.4;DISTRIBUTION OF THE mRNA;768
17.13.5;PROCESSING OF THE PRECURSOR;769
17.13.6;RECEPTORS AND SIGNALING CASCADES;769
17.13.7;INFORMATION ON ACTIVE AND/OR SOLUTION CONFORMATION;770
17.13.8;BIOLOGICAL ACTIONS WITHIN THE BRAIN;770
17.13.9;PATHOPHYSIOLOGICAL IMPLICATIONS;772
17.13.10;References;773
17.14;101: Ghrelin;777
17.14.1;ABSTRACT;777
17.14.2;DISCOVERY;777
17.14.3;STRUCURE OF THE PRECURSOR AND mRNA/GENE;777
17.14.4;DISTRIBUTION OF GHRELIN mRNA;778
17.14.5;PROCESSING OF THE GHRELIN PRECURSOR;778
17.14.6;RECEPTOR;780
17.14.7;BIOLOGICAL ACTIONS WITHIN THE BRAIN;780
17.14.8;PATHOPHYSIOLOGICAL IMPLICATIONS;780
17.14.9;References;781
17.15;102: Neurotensin;783
17.15.1;ABSTRACT;783
17.15.2;DISCOVERY OF NEUROTENSIN;783
17.15.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;783
17.15.4;NT/N mRNA EXPRESSION IN BRAIN;784
17.15.5;PROCESSING OF THE PRECURSOR;784
17.15.6;RECEPTORS AND SIGNALING CASCADES;785
17.15.7;INFORMATION ON ACTIVE OR SOLUTION CONFORMATION;785
17.15.8;BRAIN FUNCTIONS;785
17.15.9;PATHOPHYSIOLOGICAL IMPLICATIONS;787
17.15.10;References;787
17.16;103: Neuromedin U (NMU): Brain Peptide;791
17.16.1;ABSTRACT;791
17.16.2;NMU DISCOVERY;791
17.16.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;791
17.16.4;NMU DISTRIBUTION AND PROCESSING;791
17.16.5;NMU RECEPTORS;792
17.16.6;NMU1R;793
17.16.7;NMU2R;793
17.16.8;BIOLOGICAL ACTIONS OF NMU IN THE BRAIN;794
17.16.9;PATHOPHYSIOLOGICAL IMPLICATIONS;796
17.16.10;References;796
17.17;104: Galanin and GALP Systems in Brain—Molecular Pharmacology, Anatomy, and Putative Roles in Physiology and Pathology;799
17.17.1;ABSTRACT;799
17.17.2;DISCOVERY OF GALANIN AND GALANINLIKE PEPTIDE (GALP);799
17.17.3;STRUCTURE AND REGULATION OF THE GALANIN AND GALP GENES;799
17.17.4;DISTRIBUTION OF GALANIN AND GALP mRNA AND PEPTIDE-IMMUNOREACTIVITY;800
17.17.5;NATURE AND PROCESSING OF GALANIN AND GALP PRECURSORS;800
17.17.6;GALANIN FAMILY RECEPTORS;801
17.17.7;CENTRAL ACTIONS OF GALANIN AND GALP IN NORMAL AND PATHOPHYSIOLOGY;802
17.17.8;References;806
17.18;105: Brain Tachykinins;809
17.18.1;ABSTRACT;809
17.18.2;DISCOVERY;809
17.18.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;809
17.18.4;DISTRIBUTION OF THE mRNA;810
17.18.5;PROCESSING OF THE PRECURSOR;812
17.18.6;RECEPTORS AND SIGNALING CASCADES;813
17.18.7;ACTIVE AND SOLUTION CONFORMATION;813
17.18.8;BIOLOGICAL ACTIONS WITHIN THE BRAIN;814
17.18.9;PATHOPHYSIOLOGICAL IMPLICATIONS;815
17.18.10;References;815
17.19;106: CGRP and Adrenomedullin in the Brain;817
17.19.1;ABSTRACT;817
17.19.2;DISCOVERY;817
17.19.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;817
17.19.4;DISTRIBUTION OF THE mRNA/PEPTIDE;819
17.19.5;CGRP;819
17.19.6;PROCESSING OF THE PRECURSOR;820
17.19.7;RECEPTORS AND SIGNALING CASCADES;821
17.19.8;PEPTIDE CONFORMATION;822
17.19.9;BIOLOGICAL ACTIONS WITHIN THE BRAIN;822
17.19.10;CGRP;822
17.19.11;PATHOLOGICAL IMPLICATIONS;823
17.19.12;Acknowledgments;823
17.19.13;References;823
17.20;107: The RFamide-Related Peptides;825
17.20.1;ABSTRACT;825
17.20.2;DISCOVERY OF THE MAMMALIAN RFAMIDERELATED PEPTIDES;825
17.20.3;STRUCTURE OF THE RFAMIDE-RELATED PEPTIDE PRECURSORS;825
17.20.4;PROCESSING OF THE RFAMIDE-RELATED PEPTIDE PRECURSORS;827
17.20.5;DISTRIBUTION OF RFAMIDE-RELATED PEPTIDES IN THE BRAIN;827
17.20.6;RFAMIDE-RELATED PEPTIDE RECEPTORS;829
17.20.7;INFORMATION ON SOLUTION CONFORMATION OF RFAMIDERELATED PEPTIDES;829
17.20.8;BIOLOGICAL ACTIONS OF RFAMIDERELATED PEPTIDES WITHIN THE BRAIN AND PITUITARY;829
17.20.9;References;830
17.21;108: Apelin: Discovery, Distribution, and Physiological Role;833
17.21.1;ABSTRACT;833
17.21.2;DISCOVERY;833
17.21.3;STRUCTURE OF THE PRECURSOR mRNA/GENE AND PROCESSING OF THE PRECURSOR;834
17.21.4;RECEPTORS AND SIGNALING CASCADES;834
17.21.5;DISTRIBUTION OF APELIN AND ITS RECEPTOR IN THE RAT BRAIN;835
17.21.6;BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY GLAND;835
17.21.7;PERIPHERAL CARDIOVASCULAR ACTIONS;838
17.21.8;CONCLUSION;838
17.21.9;Acknowledgments;838
17.21.10;References;838
17.22;109: Urotensin II and Urotensin II–Related Peptide;841
17.22.1;ABSTRACT;841
17.22.2;DISCOVERY;841
17.22.3;STRUCTURE;841
17.22.4;LOCALIZATION;842
17.22.5;RECEPTORS AND SIGNALING CASCADES;845
17.22.6;BIOLOGICAL ACTIONS WITHIN THE BRAIN;845
17.22.7;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL SIGNIFICANCE;846
17.22.8;References;846
17.23;110: Brain/B-Type Natriuretic Peptide (BNP) and C-Type Natriuretic Peptide (CNP);851
17.23.1;ABSTRACT;851
17.23.2;DISCOVERY;851
17.23.3;STRUCTURE OF THE PRECURSOR mRNA AND GENE;853
17.23.4;DISTRIBUTION OF mRNA;853
17.23.5;PROCESSING OF PRECURSOR;855
17.23.6;RECEPTORS AND SIGNALING CASCADE;855
17.23.7;BIOLOGICAL ACTIONS IN THE BRAIN;856
17.23.8;PATHOPHYSIOLOGICAL IMPLICATIONS;856
17.23.9;References;857
17.24;111: Endozepines;859
17.24.1;ABSTRACT;859
17.24.2;DISCOVERY;859
17.24.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;859
17.24.4;DISTRIBUTION OF DBI mRNA AND ENDOZEPINE IMMUNOREACTIVITY;859
17.24.5;PROCESSING OF DBI;861
17.24.6;RECEPTORS AND SIGNALING CASCADES;861
17.24.7;CONTROL OF BIOSYNTHESIS AND RELEASE OF ENDOZEPINES;862
17.24.8;INFORMATION ON SOLUTION CONFORMATION OF ENDOZEPINES;862
17.24.9;BIOLOGICAL ACTIONS OF ENDOZEPINES WITHIN THE BRAIN;863
17.24.10;PATHOPHYSIOLOGICAL IMPLICATIONS;863
17.24.11;References;864
17.25;112: KiSS-1/Metastin;867
17.25.1;ABSTRACT;867
17.25.2;DISCOVERY OF KiSS-1 SYSTEM;867
17.25.3;STRUCTURE OF THE KiSS-1 GENE;868
17.25.4;PROCESSING OF KiSS-1 PRECURSOR: THE KISSPEPTINS;868
17.25.5;DISTRIBUTION OF KiSS-1 mRNA/PROTEIN WITHIN THE BRAIN;868
17.25.6;GPR54 AS RECEPTOR FOR KISSPEPTINS: STRUCTURE AND SIGNALING CASCADES;870
17.25.7;BIOLOGICAL ACTIONS OF KiSSPEPTINS: BRAIN AND PITUITARY EFFECTS;870
17.25.8;PATHOPHYSIOLOGICAL IMPLICATIONS;872
17.25.9;Acknowledgments;873
17.25.10;References;873
18;XI: Endocrine Peptides Section;875
18.1;113: Role of Opioid Peptides in the Local Regulation of Endocrine Glands;875
18.1.1;ABSTRACT;875
18.1.2;INTRODUCTION;875
18.1.3;PITUITARY GLAND;875
18.1.4;PANCREATIC ISLETS;876
18.1.5;ADRENAL GLAND;876
18.1.6;CONCLUSION;877
18.1.7;References;877
18.2;114: Role of Tachykinin-Gene-Related Peptides in the Local Regulation of Endocrine Glands;879
18.2.1;ABSTRACT;879
18.2.2;INTRODUCTION;879
18.2.3;PITUITARY GLAND;879
18.2.4;THYROID GLAND;880
18.2.5;PARATHYROID GLAND;880
18.2.6;PANCREATIC ISLETS;880
18.2.7;ADRENAL GLAND;881
18.2.8;LEYDIG CELLS;881
18.2.9;OVARY;882
18.2.10;CONCLUSION;882
18.2.11;References;882
18.3;115: Neuropeptide Y and the Regulation of Endocrine Function;885
18.3.1;ABSTRACT;885
18.3.2;INTRODUCTION;885
18.3.3;NPY AND ADRENAL FUNCTION;885
18.3.4;NPY IN THE PANCREAS;886
18.3.5;NPY AND GONADAL FUNCTION;887
18.3.6;NPY AND THYROID FUNCTION;888
18.3.7;CONCLUSION;889
18.3.8;References;889
18.4;116: Effects of PACAP in the Local Regulation of Endocrine Glands;893
18.4.1;ABSTRACT;893
18.4.2;INTRODUCTION;893
18.4.3;EFFECTS ON THE PITUITARY GLAND;893
18.4.4;EFFECTS ON THE THYROID GLAND;895
18.4.5;EFFECTS OF PACAP ON THE ENDOCRINE TESTIS AND OVARY;895
18.4.6;EFFECTS OF PACAP ON THE ADRENAL;895
18.4.7;EFFECTS OF PACAP ON PANCREATIC ISLETS;896
18.4.8;References;897
18.5;117: Endothelins in the Local Regulation of Endocrine Glands;901
18.5.1;ABSTRACT;901
18.5.2;INTRODUCTION;901
18.5.3;PITUITARY GLAND;901
18.5.4;THYROID GLAND;902
18.5.5;PARATHYROID GLAND;902
18.5.6;PANCREATIC ISLETS;903
18.5.7;ADRENAL GLAND;903
18.5.8;LEYDIG CELLS;904
18.5.9;OVARY;904
18.5.10;CONCLUSION;905
18.5.11;References;905
18.6;118: Adrenomedullin and Related Peptides in the Local Regulation of Endocrine Glands;907
18.6.1;ABSTRACT;907
18.6.2;INTRODUCTION;907
18.6.3;PITUITARY;907
18.6.4;ADRENALS;908
18.6.5;ENDOCRINE PANCREAS;909
18.6.6;DIFFUSE ENDOCRINE SYSTEM OF THE GUT;910
18.6.7;OTHER ENDOCRINE ORGANS;910
18.6.8;CONCLUSION;911
18.6.9;Acknowledgments;911
18.6.10;References;911
18.7;119: Ghrelin in the Local Regulation of Endocrine Glands;915
18.7.1;ABSTRACT;915
18.7.2;INTRODUCTION;915
18.7.3;GHRELIN AND THE PITUITARY;915
18.7.4;GHRELIN AND THE THYROID;916
18.7.5;GHRELIN AND THE HEART AND CARDIOMYOCYTES;916
18.7.6;GHRELIN—A NOVEL PEPTIDE FOR CARTILAGE AND BONE HOMEOSTASIS;917
18.7.7;GHRELIN AND THE PANCREAS;917
18.7.8;GHRELIN AND THE ADRENAL CORTEX;918
18.7.9;GHRELIN AND THE REPRODUCTIVE SYSTEM;918
18.7.10;CONCLUSION;919
18.7.11;Acknowledgments;919
18.7.12;References;919
18.8;120: Atrial Natriuretic Peptide in Local Regulation of Endocrine Glands;923
18.8.1;ABSTRACT;923
18.8.2;DISCOVERY;923
18.8.3;STRUCTURE OF THE PRECURSOR mRNA GENE;923
18.8.4;DISTRIBUTION OF ANP mRNA;924
18.8.5;PROCESSING;924
18.8.6;RELEASE OF NPs;925
18.8.7;RECEPTORS AND SIGNALING CASCADE;925
18.8.8;BIOLOGICAL ACTIVITIES OF NPs;925
18.8.9;PATHOPHYSIOLOGICAL IMPLICATIONS;927
18.8.10;References;927
18.9;121: Galanin, Neurotensin, and Neuromedins in the Local Regulation of Endocrine Glands;929
18.9.1;ABSTRACT;929
18.9.2;INTRODUCTION;929
18.9.3;GALANIN;929
18.9.4;NEUROTENSIN;931
18.9.5;NEUROMEDINS;932
18.9.6;CONCLUSION;932
18.9.7;References;933
19;XII: Ingestive Peptides Section;935
19.1;122: Neuropeptide Y: A Conductor of the Appetite-Regulating Orchestra in the Hypothalamus;935
19.1.1;ABSTRACT;935
19.1.2;INTRODUCTION;935
19.1.3;NPY AND APPETITE;935
19.1.4;MECHANISM OF ACTION;936
19.1.5;REGULATION OF NPY SIGNALING AND APPETITE;937
19.1.6;PATHOPHYSIOLOGY;938
19.1.7;Acknowledgment;939
19.1.8;References;939
19.2;123: Hypothalamic Galanin and Ingestive Behavior: Relation to Dietary Fat, Alcohol, and Circulating Lipids;941
19.2.1;ABSTRACT;941
19.2.2;STIMULATORY EFFECTS OF GAL INJECTION ON INGESTIVE BEHAVIOR;941
19.2.3;EFFECTS PRODUCED BY MUTATIONS OF THE GAL GENE OR GAL RECEPTOR GENES;942
19.2.4;EFFECTS OF CIRCULATING HORMONES AND DIETARY CONDITIONS ON ENDOGENOUS GAL;942
19.2.5;SITES OF ACTION AND NEURAL NETWORKS AFFECTED;943
19.2.6;RECEPTORS AND SIGNALING PATHWAYS MEDIATING GAL EFFECTS ON INGESTIVE BEHAVIOR;944
19.2.7;GAL IN RELATION TO OTHER PEPTIDERGIC AND AMINERGIC SYSTEMS CONTROLLING INGESTIVE BEHAVIOR;944
19.2.8;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONSEQUENCES OF GAL’S ACTIONS;944
19.2.9;Acknowledgments;945
19.2.10;References;945
19.3;124: Effects of Melanocortins on Ingestive Behavior;949
19.3.1;ABSTRACT;949
19.3.2;EFFECTS OF THE MELANOCORTINS ON FEEDING BEHAVIOR;949
19.3.3;GENETIC STUDIES ON MELANOCORTIN ACTION;950
19.3.4;FUNCTIONAL RESPONSE OF THE MELANOCORTINS TO DIFFERING METABOLIC AND FEEDING STATES;951
19.3.5;NEUROANATOMY OF THE CENTRAL MELANOCORTIN SYSTEM;953
19.3.6;RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR MELANOCORTIN ACTIONS ON INGESTIVE BEHAVIOR;954
19.3.7;INTERACTIONS OF THE MELANOCORTINS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS;955
19.3.8;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;955
19.3.9;References;956
19.4;125: CART Peptide and Ingestive Behavior;959
19.4.1;ABSTRACT;959
19.4.2;DESCRIPTION OF CART PEPTIDE EFFECTS ON FEEDING BEHAVIOR;959
19.4.3;STUDIES FROM GENETIC MANIPULATIONS OR MUTATIONS;959
19.4.4;FUNCTIONAL RESPONSE OF CART TO DIFFERING METABOLIC AND FEEDING STATES;960
19.4.5;SITES OF ACTION AND NEURAL NETWORKS AFFECTED;960
19.4.6;RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR INGESTIVE BEHAVIORS;961
19.4.7;INTERACTIONS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS;961
19.4.8;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;962
19.4.9;References;962
19.5;126: Orexins and Opioids in Feeding Behavior;965
19.5.1;ABSTRACT;965
19.5.2;EFFECT OF OREXINS AND OPIOIDS ON FEEDING BEHAVIOR;965
19.5.3;STUDIES FROM GENETIC MANIPULATIONS OR MUTATIONS;967
19.5.4;FUNCTIONAL RESPONSE OF OREXINS AND OPIOIDS TO METABOLIC AND FEEDING STATES;967
19.5.5;OxA AND OPIOID LIGANDS AND RECEPTORS: SITES OF ACTION AND NEURAL NETWORKS AFFECTED;968
19.5.6;INTERACTIONS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS;969
19.5.7;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;969
19.5.8;INTERACTION BETWEEN OxA AND OPIOIDS;970
19.5.9;CONCLUSION;970
19.5.10;References;970
19.6;127: Melanin-Concentrating Hormone;975
19.6.1;ABSTRACT;975
19.6.2;INTRODUCTION;975
19.6.3;EFFECTS OF MCH ON FEEDING BEHAVIOR;975
19.6.4;STUDIES FROM GENETIC MANIPULATIONS OR MUTATIONS;976
19.6.5;FUNCTIONAL RESPONSE OF THE PEPTIDE/GENE TO DIFFERING METABOLIC AND FEEDING STATES;976
19.6.6;SITES OF ACTION AND NEURAL NETWORKS AFFECTED;977
19.6.7;RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR THE INGESTIVE EFFECTS;978
19.6.8;INTERACTIONS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS;978
19.6.9;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;978
19.6.10;References;979
19.7;128: Corticotrophin-Releasing Hormone (CRH) and Ingestive Behavior;983
19.7.1;ABSTRACT;983
19.7.2;EFFECTS OF CRH AND UROCORTINS ON FEEDING BEHAVIOR;983
19.7.3;STUDIES FROM GENETIC MANIPULATIONS;984
19.7.4;METABOLIC REGULATION OF CRH AND CRH RECEPTORS;984
19.7.5;SITES OF ACTION AND NETWORKS MEDIATING CRH EFFECTS;984
19.7.6;RECEPTORS AND PATHWAYS MEDIATING THE EFFECTS OF CRH AND THE UROCORTINS ON FOOD INTAKE;985
19.7.7;INTERACTIONS WITH NEUROPEPTIDE SYSTEMS;985
19.7.8;PHYSIOLOGY AND PATHOPHYSIOLOGICAL IMPLICATIONS;986
19.7.9;References;986
19.8;129: Peptide YY (PYY) and Neuromedin U (NMU): Effects on Ingestive Behavior;991
19.8.1;ABSTRACT;991
19.8.2;INTRODUCTION;991
19.8.3;DISCOVERY;992
19.8.4;DISTRIBUTION AND RELEASE;992
19.8.5;RECEPTORS;992
19.8.6;THE ROLE OF NMU IN THE REGULATION OF ENERGY BALANCE;993
19.8.7;PYY;994
19.8.8;CONCLUSION;995
19.8.9;References;995
19.9;130: Ghrelin and Ingestive Behavior;999
19.9.1;ABSTRACT;999
19.9.2;GHRELIN ADMINISTRATION INDUCES FOOD INTAKE ACROSS SPECIES;999
19.9.3;THE GROWTH HORMONE SECRETAGOGUE RECEPTOR GHSR-1a MEDIATES GHRELIN-INDUCED FOOD INTAKE;1000
19.9.4;GHRELIN TARGETS THE HYPOTHALAMUS TO INCREASE FOOD INTAKE AND BODY WEIGHT;1000
19.9.5;OTHER HYPOTHALAMIC PATHWAYS INVOLVED IN GHRELIN-INDUCED HYPERPHAGIA;1001
19.9.6;EXTRA-HYPOTHALAMIC EFFECTS OF GHRELIN ON FOOD INTAKE;1002
19.9.7;PERIPHERAL GHRELIN LEVELS ARE REGULATED BY FOOD INTAKE;1002
19.9.8;References;1004
19.10;131: Cholecystokinin and Satiety;1007
19.10.1;ABSTRACT;1007
19.10.2;INTRODUCTION;1007
19.10.3;FEEDING ACTIONS OF PERIPHERAL CCK;1007
19.10.4;FEEDING ACTIONS OF CENTRAL CCK;1009
19.10.5;STUDIES WITH OLETF RATS AND CCK-A RECEPTOR KNOCKOUT MICE;1009
19.10.6;FUNCTIONAL RESPONSES TO PERIPHERAL CCK IN DIFFERING METABOLIC STATES;1010
19.10.7;SITES OF ACTION FOR PERIPHERAL CCK IN SATIETY;1011
19.10.8;RECEPTORS AND SIGNALING PATHWAYS MEDIATING CCK SATIETY;1011
19.10.9;INTERACTIONS WITH OTHER SIGNALING SYSTEMS;1012
19.10.10;PATHOPHYSIOLOGIAL IMPLICATIONS;1012
19.10.11;References;1012
19.11;132: Enterostatin, a Peptide Regulator of Dietary Fat Ingestion;1015
19.11.1;ABSTRACT;1015
19.11.2;INTRODUCTION;1015
19.11.3;ENTEROSTATIN EFFECTS ON FEEDING BEHAVIOR;1015
19.11.4;GENOMIC STUDIES;1016
19.11.5;FUNCTIONAL RESPONSES TO DIFFERING FEEDING AND METABOLIC CONDITIONS;1016
19.11.6;SITES OF ACTION AND NEURAL NETWORKS AFFECTED;1017
19.11.7;RECEPTORS AND SIGNALING PATHWAYS;1018
19.11.8;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;1019
19.11.9;References;1019
19.12;133: Regulation of Feeding Behavior by Glucagonlike Peptide 1 (GLP-1);1021
19.12.1;ABSTRACT;1021
19.12.2;EFFECTS OF GLP-1 ON FEEDING BEHAVIOR;1021
19.12.3;STUDIES FROM GENETIC MANIPULATIONS (KNOCKOUTS, TRANSGENICS) AND SYNTHETIC ANALOGS;1021
19.12.4;FUNCTIONAL RESPONSE OF THE GLP-1 PEPTIDE/GENE TO DIFFERING METABOLIC AND FEEDING STATES;1022
19.12.5;SITES OF ACTION AND NEURAL NETWORKS AFFECTED BY GLP-1;1022
19.12.6;GLP-1 RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR THE INGESTIVE EFFECTS;1022
19.12.7;INTERACTIONS OF GLP-1 WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS;1023
19.12.8;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;1023
19.12.9;References;1024
19.13;134: Role of Amylin and Calcitonin-Gene-Related Peptide (CGRP) in the Control of Food Intake;1027
19.13.1;ABSTRACT;1027
19.13.2;INTRODUCTION;1027
19.13.3;CHARACTERIZATION OF THE EFFECTS OF AMYLIN AND CGRP ON FOOD INTAKE;1027
19.13.4;FOOD INTAKE IN KNOCKOUT ANIMALS;1028
19.13.5;FOOD INTAKE IN ANIMALS OVEREXPRESSING AMYLIN;1029
19.13.6;FOOD INTAKE IN ANIMALS DEFICIENT OF CGRP OR OVEREXPRESSING CGRP;1029
19.13.7;REGULATION OF AMYLIN AND CGRP SYNTHESIS AND SECRETION;1029
19.13.8;CENTRAL PATHWAYS MEDIATING THE ANORECTIC EFFECTS OF AMYLIN AND CGRP;1029
19.13.9;HYPOTHALAMIC INVOLVEMENT IN THE ANORECTIC ACTION OF PERIPHERAL AMYLIN;1030
19.13.10;RECEPTORS AND SIGNALING PATHWAYS;1030
19.13.11;INTERACTION WITH OTHER PEPTIDES REGULATING INGESTIVE BEHAVIOR;1031
19.13.12;INTERACTION BETWEEN AMYLIN AND METABOLITES;1031
19.13.13;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;1031
19.13.14;CONCLUSION;1031
19.13.15;References;1031
19.14;135: Leptin and the Regulation of Feeding;1033
19.14.1;ABSTRACT;1033
19.14.2;LEPTIN AND FEEDING BEHAVIOR;1033
19.14.3;THE ABSENCE OF LEPTIN ACTION;1033
19.14.4;FUNCTIONAL RESPONSES TO LEPTIN DURING ALTERED METABOLIC STATES;1034
19.14.5;SITES OF LEPTIN ACTION;1034
19.14.6;LEPTIN RECEPTORS AND INTRACELLULAR SIGNALING PATHWAYS;1034
19.14.7;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;1036
19.14.8;References;1037
19.15;136: Ingestive Peptides: Insulin;1039
19.15.1;ABSTRACT;1039
19.15.2;INTRODUCTION;1039
19.15.3;EFFECTS OF INSULIN ON FEEDING BEHAVIOR;1039
19.15.4;GENETIC AND MOLECULAR BIOLOGICAL MANIPULATIONS;1041
19.15.5;METABOLIC STATES;1041
19.15.6;SITE OF ACTION AND NEURAL NETWORKS AFFECTED;1042
19.15.7;RECEPTORS AND SIGNALING PATHWAYS;1042
19.15.8;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS;1042
19.15.9;CONCLUSION;1043
19.15.10;References;1043
20;XIII: Gastrointestinal Peptides Section;1045
20.1;137: Adrenomedullin in Gastrointestinal Function;1045
20.1.1;ABSTRACT;1045
20.1.2;INTRODUCTION;1045
20.1.3;STRUCTURE;1045
20.1.4;EXPRESSION AND DISTRIBUTION;1046
20.1.5;RELEASE;1046
20.1.6;RECEPTORS AND SIGNAL TRANSDUCTION PATHWAYS;1046
20.1.7;BIOLOGICAL ACTIONS;1047
20.1.8;CONCLUSION;1048
20.1.9;Acknowledgment;1048
20.1.10;References;1048
20.2;138: Calcitonin Gene-Related Peptide and Gastrointestinal Function;1051
20.2.1;ABSTRACT;1051
20.2.2;INTRODUCTION;1051
20.2.3;DISTRIBUTION OF CGRP IN THE GI TRACT;1051
20.2.4;CGRP RECEPTORS IN THE GI TRACT;1052
20.2.5;RELEASE OF CGRP IN THE GI TRACT;1053
20.2.6;PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS OF CGRP IN THE GI TRACT;1053
20.2.7;References;1056
20.3;139: Peripheral Cholecystokinin;1059
20.3.1;ABSTRACT;1059
20.3.2;DISCOVERY;1059
20.3.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;1060
20.3.4;CHOLECYSTOKININ PEPTIDE DISTRIBUTION;1060
20.3.5;PROCESSING OF PREPROCHOLECYSTOKININ;1060
20.3.6;MOLECULAR FORMS OF CHOLECYSTOKININ;1062
20.3.7;CHOLECYSTOKININ RECEPTORS;1062
20.3.8;SOLUTION CONFORMATION;1063
20.3.9;PERIPHERAL BIOLOGICAL ACTIONS OF CHOLECYSTOKININ;1064
20.3.10;CONCLUSION;1066
20.3.11;References;1066
20.4;140: Corticotrophin-Releasing Hormone (CRH) Family in the Gastrointestinal System;1069
20.4.1;ABSTRACT;1069
20.4.2;INTRODUCTION;1069
20.4.3;EXPRESSION AND LOCATION OF CRH PEPTIDES AND RECEPTORS IN THE GI SYSTEM;1069
20.4.4;ACTIONS OF CRH AND RELATED PEPTIDES IN GI FUNCTIONS;1070
20.4.5;NEURONAL PATHWAYS INVOLVED IN CRH ACTIONS IN GI FUNCTIONS;1072
20.4.6;PATHOPHYSIOLOGICAL IMPLICATIONS;1072
20.4.7;Acknowledgment;1073
20.4.8;References;1073
20.5;141: Paneth Cell a-Defensins;1075
20.5.1;ABSTRACT;1075
20.5.2;DISCOVERY OF ENTERIC PANETH CELL a-DEFENSINS;1075
20.5.3;a-DEFENSIN GENE AND PRECURSOR STRUCTURES;1076
20.5.4;DISTRIBUTION OF a-DEFENSINS IN THE GASTROINTESTINAL TRACT;1078
20.5.5;STRUCTURES OF PANETH CELL a-DEFENSINS;1078
20.5.6;MECHANISMS OF ACTION;1078
20.5.7;PATHOPHYSIOLOGICAL IMPLICATIONS;1080
20.5.8;Acknowledgments;1080
20.5.9;References;1080
20.6;142: Galanin in the Gastrointestinal Tract: Distribution and Function;1083
20.6.1;ABSTRACT;1083
20.6.2;INTRODUCTION;1083
20.6.3;GALANIN DISTRIBUTION;1083
20.6.4;BIOLOGICAL EFFECTS OF GALANIN IN THE GASTROINTESTINAL TRACT;1084
20.6.5;GALANIN RECEPTORS;1084
20.6.6;INFLAMMATION AND INJURY;1087
20.6.7;Acknowledgment;1087
20.6.8;References;1087
20.7;143: Gastrin;1089
20.7.1;ABSTRACT;1089
20.7.2;DISCOVERY;1089
20.7.3;STRUCTURE OF THE GENE AND PRECURSOR;1089
20.7.4;DISTRIBUTION OF MRNA IN GUT;1090
20.7.5;RECEPTOR EXPRESSION AND REGULATION;1090
20.7.6;BIOLOGICAL ACTIONS ON GI TRACT;1090
20.7.7;PATHOPHYSIOLOGICAL IMPLICATIONS;1091
20.7.8;References;1091
20.8;144: Gastrin-Releasing Peptide;1093
20.8.1;ABSTRACT;1093
20.8.2;INTRODUCTION;1093
20.8.3;STRUCTURE OF THE PRECURSOR mRNA/GENE AND PEPTIDE VARIANTS;1093
20.8.4;DISTRIBUTION OF GRP-LIKE IMMUNOREACTIVITY, GRP mRNA, AND GRP RECEPTOR;1094
20.8.5;RECEPTOR SUBTYPES AND SIGNALING;1095
20.8.6;BIOLOGICAL ACTIONS WITHIN THE GI TRACT;1095
20.8.7;PATHOPHYSIOLOGICAL IMPLICATIONS;1099
20.8.8;References;1100
20.9;145: Glucagonlike Peptides 1 and 2, Enteroglucagon, Glicentin, and Oxyntomodulin;1103
20.9.1;ABSTRACT;1103
20.9.2;DISCOVERY AND STRUCTURE OF THE GENE;1103
20.9.3;EXPRESSION OF THE GENE;1104
20.9.4;ACTIVE CONFORMATION AND METABOLISM;1105
20.9.5;RECEPTOR EXPRESSION;1105
20.9.6;BIOLOGICAL ACTIONS;1106
20.9.7;ACTIONS OF GLP-1;1106
20.9.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1109
20.9.9;References;1110
20.10;146: Ghrelin;1111
20.10.1;ABSTRACT;1111
20.10.2;ALTERNATIVE DISCOVERIES OF GHRELIN;1111
20.10.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;1111
20.10.4;DISTRIBUTION IN THE GASTROINTESTINAL TRACT;1112
20.10.5;STRUCTURE–ACTIVITY RELATIONS OF GHRELIN AND OF THE GHRELIN RECEPTOR;1112
20.10.6;BIOLOGICAL ACTION ON THE GASTROINTESTINAL TRACT;1113
20.10.7;PATHOPHYSIOLOGICAL IMPLICATIONS AND THERAPEUTIC POTENTIAL;1114
20.10.8;Acknowledgments;1115
20.10.9;References;1115
20.11;147: Leptin and the Gastrointestinal Tract;1117
20.11.1;ABSTRACT;1117
20.11.2;INTRODUCTION;1117
20.11.3;THE STOMACH PRODUCES LEPTIN;1117
20.11.4;GASTRIC LEPTIN IS A NEUROENDOCRINE MOLECULE FOR SATIETY;1118
20.11.5;GASTRIC LEPTIN ENTERS THE INTESTINE;1118
20.11.6;LEPTIN REGULATES INTESTINAL ENDOCRINE SECRETIONS;1118
20.11.7;GUT LEPTIN AND INTESTINAL ABSORPTION OF NUTRIENTS;1119
20.11.8;LEPTIN AND GUT PATHOLOGIES;1120
20.11.9;CONCLUSION;1120
20.11.10;Acknowledgments;1121
20.11.11;References;1121
20.12;148: Motilin;1123
20.12.1;ABSTRACT;1123
20.12.2;DISCOVERY OF MOTILIN;1123
20.12.3;STRUCTURE OF MOTILIN AND RELATED PEPTIDES;1123
20.12.4;DISTRIBUTION IN THE GI TRACT;1125
20.12.5;STRUCTURE–ACTIVITY;1126
20.12.6;RECEPTOR;1126
20.12.7;BIOLOGICAL ACTIONS;1127
20.12.8;PATHOPHYSIOLOGICAL IMPLICATION;1129
20.12.9;Acknowledgments;1129
20.12.10;References;1130
20.13;149: Neurotensin in Regulation of Gastrointestinal Functions;1131
20.13.1;ABSTRACT;1131
20.13.2;INTRODUCTION;1131
20.13.3;NT INHIBITS MOTILITY AND SECRETION IN THE STOMACH AND SMALL INTESTINE;1132
20.13.4;NT ENHANCES COLONIC MOTILITY AND STIMULATES SECRETION;1132
20.13.5;ROLE OF NT AND NTR1 IN INTESTINAL INFLAMMATION;1133
20.13.6;NT PROMOTES CELL GROWTH, REGENERATION, AND HEALING OF THE GI MUCOSA;1133
20.13.7;NT AND COLONIC STRESS RESPONSES;1133
20.13.8;CONCLUSION;1134
20.13.9;References;1134
20.14;150: Pituitary Adenylate Cyclase Activating Polypeptide (PACAP);1137
20.14.1;ABSTRACT;1137
20.14.2;PACAP IS A NEWLY DISCOVERED NEUROENTERIC PEPTIDE;1137
20.14.3;CLONING AND CHARACTERIZATION OF PAC1;1137
20.14.4;SIGNAL TRANSDUCTION OF PAC1;1138
20.14.5;LOCALIZATION OF PAC1;1138
20.14.6;PHYSIOLOGY OF PAC1 IN THE GASTROINTESTINAL TRACT;1139
20.14.7;CONCLUSION;1140
20.14.8;Acknowledgments;1140
20.14.9;References;1140
20.15;151: Pancreatic Polypeptide;1143
20.15.1;ABSTRACT;1143
20.15.2;DISCOVERY OF PANCREATIC POLYPEPTIDE AS IT RELATES TO THE GASTROINTESTINAL TRACT;1143
20.15.3;STRUCTURE OF THE PRECURSOR mRNA/GENE AND PEPTIDE VARIANTS;1144
20.15.4;DISTRIBUTION OF THE mRNA AND PROTEIN;1144
20.15.5;RECEPTOR SUBTYPES, SIGNALING, AND DISTRIBUTION;1145
20.15.6;BIOLOGICAL ACTIONS;1147
20.15.7;PHYSIOPATHOLOGICAL IMPLICATIONS;1149
20.15.8;References;1150
20.16;152: Peptide YY;1155
20.16.1;ABSTRACT;1155
20.16.2;INTRODUCTION;1155
20.16.3;STRUCTURE OF THE PYY GENE AND PYY BIOSYNTHESIS;1155
20.16.4;GASTROINTESTINAL DISTRIBUTION AND ONTOGENY OF INTESTINAL PYY;1155
20.16.5;REGULATION OF PYY SECRETION;1156
20.16.6;PYY RECEPTORS;1157
20.16.7;BIOLOGICAL ACTIONS ON THE GASTROINTESTINAL TRACT;1158
20.16.8;GROWTH PROMOTING ACTIONS OF PYY ON THE GASTROINTESTINAL TRACT;1159
20.16.9;INHIBITORY ACTION OF PYY(3–36) ON APPETITE AND FOOD INTAKE;1159
20.16.10;PATHOPHYSIOLOGY OF PYY;1159
20.16.11;References;1159
20.17;153: Secretin;1161
20.17.1;ABSTRACT;1161
20.17.2;DISCOVERY OF SECRETIN;1161
20.17.3;STRUCTURE OF SECRETIN, ITS PRECURSOR TRANSCRIPT, AND GENE;1161
20.17.4;DISTRIBUTION OF SECRETIN AND ITS mRNA;1162
20.17.5;SECRETIN RECEPTOR SUBTYPES, DISTRIBUTION, AND SIGNALING;1164
20.17.6;BIOLOGICAL ACTIONS OF SECRETIN IN THE GASTROINTESTINAL TRACT;1164
20.17.7;PATHOPHYSIOLOGY AND CLINICAL APPLICATION OF SECRETIN;1167
20.17.8;References;1167
20.18;154: Somatostatin;1169
20.18.1;ABSTRACT;1169
20.18.2;INTRODUCTION;1169
20.18.3;SOMATOSTATIN-14, SOMATOSTATIN-28 AND CORTISTATIN IN THE GASTROINTESTINAL TRACT;1169
20.18.4;SOMATOSTATIN RECEPTORS IN THE GASTROINTESTINAL TRACT;1170
20.18.5;BIOLOGICAL ACTION OF SOMATOSTATIN IN THE GASTROINTESTINAL TRACT;1170
20.18.6;SOMATOSTATIN AND SOMATOSTATIN RECEPTORS IN THE DISEASED GASTROINTESTINAL TRACT;1171
20.18.7;SOMATOSTATIN ANALOGS AND THEIR CLINICAL APPLICATIONS IN GASTROINTESTINAL DISEASE;1172
20.18.8;References;1173
20.19;155: Somatostatin Analogs in theGastrointestinal Tract;1177
20.19.1;ABSTRACT;1177
20.19.2;INTRODUCTION;1177
20.19.3;GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS;1177
20.19.4;SECRETORY DIARRHEAS;1179
20.19.5;ESOPHAGEAL VARICEAL HEMORRHAGE;1180
20.19.6;GI MOTILITY AND FUNCTIONAL GI DISORDERS;1180
20.19.7;POSTOPERATIVE COMPLICATIONS OF SURGERY;1181
20.19.8;BILIARY SYSTEM;1182
20.19.9;References;1182
20.20;156: Substance P and Related Tachykinins in the Gastrointestinal Tract;1185
20.20.1;ABSTRACT;1185
20.20.2;DISCOVERY OF TACHYKININS IN THE GUT;1185
20.20.3;DISTRIBUTION OF TACHYKININ mRNAS AND PEPTIDES IN THE GI TRACT;1185
20.20.4;TACHYKININ RECEPTOR SUBTYPES, SIGNALING, AND DISTRIBUTION IN THE GI TRACT;1186
20.20.5;BIOLOGICAL ACTIONS OF TACHYKININS IN THE GUT;1187
20.20.6;PATHOPHYSIOLOGICAL IMPLICATIONS OF TACHYKININS IN THE GI TRACT;1188
20.20.7;Acknowledgments;1190
20.20.8;References;1191
20.21;157: TFF (Trefoil Factor Family) Peptides;1193
20.21.1;ABSTRACT;1193
20.21.2;DISCOVERY;1193
20.21.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;1193
20.21.4;EXPRESSION IN THE GI TRACT;1194
20.21.5;ACTIVE CONFORMATION, 3D STRUCTURE;1196
20.21.6;TFF RECEPTORS AND SIGNALING CASCADES;1196
20.21.7;BIOLOGICAL ACTIONS ON THE GI TRACT;1196
20.21.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1198
20.21.9;Acknowledgments;1199
20.21.10;References;1199
20.22;158: Signaling by Vasoactive Intestinal Peptide in Gastrointestinal Smooth Muscle;1201
20.22.1;ABSTRACT;1201
20.22.2;INTRODUCTION;1201
20.22.3;INTERPLAY OF INHIBITORY NEUROTRANSMITTERS;1202
20.22.4;VIP RECEPTORS AND THEIR SIGNALING IN SMOOTH MUSCLE;1202
20.22.5;Acknowledgments;1205
20.22.6;References;1205
21;XIV: Cardiovascular Peptides Section;1209
21.1;159: Adrenomedullin and Its Related Peptides;1209
21.1.1;ABSTRACT;1209
21.1.2;DISCOVERY AND STRUCTURE OF AM;1209
21.1.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;1209
21.1.4;DISTRIBUTION OF THE mRNA AND PEPTIDE IN THE CARDIOVASCULAR SYSTEM;1210
21.1.5;RECEPTORS AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM;1211
21.1.6;BIOLOGICAL ACTIONS IN THE CARDIOVASCULAR SYSTEM;1211
21.1.7;PROADRENOMEDULLIN N-TERMINAL 20 PEPTIDE;1212
21.1.8;INFORMATION ON MOLECULAR FORM OF AM;1213
21.1.9;CLINICAL IMPLICATION OF AM IN CARDIOVASCULAR DISEASES;1213
21.1.10;CONCLUSION;1213
21.1.11;References;1214
21.2;160: Angiotensin II and Its Related Peptides;1215
21.2.1;ABSTRACT;1215
21.2.2;DISCOVERY;1215
21.2.3;STRUCTURE OF THE PEPTIDE AND COMPONENT OF RA SYSTEM;1215
21.2.4;DISTRIBUTION OF RA SYSTEM, PROCESSING, AND ENDOGENOUS FORM IN THE CARDIOVASCULAR SYSTEM;1216
21.2.5;RECEPTORS AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM;1216
21.2.6;BIOLOGICAL ACTIONS AND PATHOPHYSIOLOGICAL IMPLICATION IN THE CARDIOVASCULAR SYSTEM;1217
21.2.7;References;1219
21.3;161: Bradykinin and Its Related Peptides;1221
21.3.1;ABSTRACT;1221
21.3.2;DISCOVERY;1221
21.3.3;STRUCTURE OF KININOGEN mRNA AND GENE;1221
21.3.4;DISTRIBUTION OF KININOGEN AND KALLIKREIN mRNA AND KININ PEPTIDES;1222
21.3.5;FORMATION OF KININ PEPTIDES;1222
21.3.6;METABOLISM OF KININ PEPTIDES;1223
21.3.7;KININ RECEPTORS AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM;1224
21.3.8;ROLE OF KININ PEPTIDES IN HEALTH AND DISEASE STATES;1224
21.3.9;References;1224
21.4;162: Calcitonin Gene-Related Peptides;1227
21.4.1;ABSTRACT;1227
21.4.2;CALCITONIN GENE-RELATED PEPTIDE;1227
21.4.3;Acknowledgments;1230
21.4.4;References;1230
21.5;163: Endothelins;1233
21.5.1;ABSTRACT;1233
21.5.2;DISCOVERY;1233
21.5.3;STRUCTURE OF THE PRECURSOR mRNA/GENE AND PROCESSING;1233
21.5.4;PLASMA CONCENTRATION AND INACTIVATION OF ENDOTHELIN 1;1235
21.5.5;RECEPTORS AND THEIR DISTRIBUTION;1236
21.5.6;BIOLOGICAL ACTIONS IN THE CARDIOVASCULAR SYSTEM;1237
21.5.7;References;1238
21.6;164: Ghrelin: Its Therapeutic Potential in Heart Failure;1239
21.6.1;ABSTRACT;1239
21.6.2;INTRODUCTION;1239
21.6.3;DISCOVERY, STRUCTURE, AND SYNTHESIS;1240
21.6.4;RECEPTORS AND THEIR DISTRIBUTION;1240
21.6.5;BIOLOGICAL ACTINS;1240
21.6.6;CLINICAL APPLICATION OF GHRELIN;1241
21.6.7;CONCLUSION;1242
21.6.8;References;1242
21.7;165: Natriuretic Peptides in the Cardiovascular System;1245
21.7.1;ABSTRACT;1245
21.7.2;DISCOVERY OF NATRIURETIC PEPTIDES;1245
21.7.3;STRUCTURE OF THE PRECURSORS, mRNAs, AND GENES OF NPs;1246
21.7.4;DISTRIBUTION OF THE mRNA AND PEPTIDE IN THE CARDIOVASCULAR SYSTEM;1247
21.7.5;PROCESSING AND ENDOGENOUS FORMS OF NPs;1248
21.7.6;RECEPTORS OF NPs AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM;1248
21.7.7;INFORMATION ON ACTIVE AND/OR SOLUTION CONFORMATION OF NPs;1249
21.7.8;BIOLOGICAL ACTIONS OF NPs IN THE CARDIOVASCULAR SYSTEM;1249
21.7.9;PATHOPHYSIOLOGICAL IMPLICATION OF NPs IN THE CARDIOVASCULAR SYSTEM;1250
21.7.10;References;1252
21.8;166: Urotensin and Its Related Peptides;1255
21.8.1;ABSTRACT;1255
21.8.2;INTRODUCTION;1255
21.8.3;UROCORTIN (UROTENSIN I);1255
21.8.4;UROTENSIN II;1257
21.8.5;CONCLUSION;1258
21.8.6;References;1258
21.9;167: Vasoactive Intestinal Peptide;1261
21.9.1;ABSTRACT;1261
21.9.2;INTRODUCTION;1261
21.9.3;DISCOVERY;1262
21.9.4;DISTRIBUTION;1262
21.9.5;PROCESSING;1262
21.9.6;RECEPTORS;1263
21.9.7;BIOLOGICAL ACTIONS;1264
21.9.8;PATHOPHYSIOLOGY;1266
21.9.9;Acknowledgments;1267
21.9.10;References;1267
21.10;168: Cardiovascular Peptides: Vasopressin;1269
21.10.1;ABSTRACT;1269
21.10.2;DISCOVERY;1269
21.10.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;1269
21.10.4;DISTRIBUTION OF THE mRNA;1269
21.10.5;PROCESSING;1269
21.10.6;RECEPTORS;1270
21.10.7;ACTIVE OR SOLUTION CONFORMATION;1270
21.10.8;BIOLOGICAL ACTIVITY;1270
21.10.9;PATHOPHYSIOLOGICAL IMPLICATIONS;1271
21.10.10;References;1272
22;XV: Renal Peptides Section;1273
22.1;169: Renal Effects of Neurohypophyseal Peptides;1273
22.1.1;ABSTRACT;1273
22.1.2;BRIEF HISTORY AND OVERVIEW OF THE NEUROHYPOPHYSEAL PEPTIDES;1273
22.1.3;BODY FLUID HOMEOSTASIS;1274
22.1.4;VASOPRESSIN AND OXYTOCIN RECEPTORS;1274
22.1.5;LOCALIZATION OF VASOPRESSIN AND OXYTOCIN RECEPTORS IN THE KIDNEY;1275
22.1.6;RENAL EFFECTS OF VASOPRESSIN;1275
22.1.7;RENAL EFFECTS OF OXYTOCIN;1277
22.1.8;References;1277
22.2;170: Renal Renin-Angiotensin System;1281
22.2.1;ABSTRACT;1281
22.2.2;INTRODUCTION;1281
22.2.3;DISTRIBUTION OF RENIN, ANGIOTENSINCONVERTING ENZYME, AND ANGIOTENSINOGEN IN THE KIDNEY;1281
22.2.4;INTRARENAL LEVELS OF ANGIOTENSIN II;1284
22.2.5;BIOLOGICAL ACTIONS OF INTRARENAL ANG II;1285
22.2.6;CONCLUSION;1286
22.2.7;References;1286
22.3;171: Renal Natriuretic Peptide System and Actions of Urodilatin;1289
22.3.1;ABSTRACT;1289
22.3.2;DISCOVERY AND FIRST DESCRIPTIONS OF URODILATIN;1289
22.3.3;METABOLISM OF URODILATIN IN THE KIDNEY AND ITS PHYSIOLOGICAL AND PHARMACOLOGICAL SIGNIFICANCE;1292
22.3.4;URODILATIN—CLINICAL IMPLICATIONS;1293
22.3.5;References;1294
22.4;172: ANP and Its Role in the Regulation of Renal Tubular Transport Processes;1297
22.4.1;ABSTRACT;1297
22.4.2;DISCOVERY OF ATRIAL NATRIURETIC PEPTIDE ACTIONS IN THE KIDNEY;1297
22.4.3;EFFECTS OF ANP ON TUBULAR TRANSPORT SYSTEMS;1297
22.4.4;References;1301
22.5;173: Adrenomedullin as a Renal Peptide;1303
22.5.1;ABSTRACT;1303
22.5.2;ADRENOMEDULLIN PEPTIDE;1303
22.5.3;AM RECEPTOR;1303
22.5.4;RENAL BIOLOGICAL ACTIONS OF AM;1304
22.5.5;RENOPROTECTIVE ACTIONS OF AM;1304
22.5.6;CLINICAL IMPLICATIONS OF AM IN ASSOCIATION WITH THE KIDNEY;1304
22.5.7;References;1305
22.6;174: Adrenomedullin 2/Intermedin;1309
22.6.1;ABSTRACT;1309
22.6.2;DISCOVERY;1309
22.6.3;STRUCTURE OF THE PRECURSOR mRNA AND GENE;1310
22.6.4;DISTRIBUTION OF mRNA;1312
22.6.5;PROCESSING OF THE PRECURSOR;1312
22.6.6;RECEPTORS AND SIGNALING CASCADE;1312
22.6.7;PATHOPHYSIOLOGICAL IMPLICATIONS;1313
22.6.8;References;1314
22.7;175: Renal Endothelin;1315
22.7.1;ABSTRACT;1315
22.7.2;BRIEF HISTORY OF ENDOTHELIN;1315
22.7.3;LOCALIZATION OF THE ET-1 SYSTEM IN THE KIDNEY;1315
22.7.4;RENAL HEMODYNAMIC EFFECTS OF ET-1;1316
22.7.5;ET-1 EFFECTS ON EXCRETORY FUNCTION;1316
22.7.6;RENAL ET-1 IN BLOOD PRESSURE REGULATION;1318
22.7.7;CONCLUSION;1319
22.7.8;References;1319
22.8;176: Prolactin and Kidney Function;1323
22.8.1;ABSTRACT;1323
22.8.2;INTRODUCTION;1323
22.8.3;CLASSICAL PRODUCTION SITE AND ACTIONS OF PROLACTIN;1323
22.8.4;PROLACTIN RECEPTORS;1324
22.8.5;PROLACTIN AND OSMOREGULATION;1324
22.8.6;PROLACTIN RECEPTORS IN THE MAMMALIAN KIDNEY;1324
22.8.7;RENAL PRODUCTION OF PROLACTIN;1325
22.8.8;RENAL ACTIONS OF PROLACTIN;1325
22.8.9;PROLACTIN AND RENAL FUNCTION IN HUMANS;1326
22.8.10;THE JURY IS STILL OUT ON THE RENAL ACTIONS OF PROLACTIN;1326
22.8.11;HAVE TRANSGENE METHODS CLARIFIED THE ISSUE?;1327
22.8.12;References;1327
23;XVI: Respiratory Peptides Section;1329
23.1;177: Therapeutic Potential of Adrenomedullin for Pulmonary Hypertension;1329
23.1.1;ABSTRACT;1329
23.1.2;INTRODUCTION;1329
23.1.3;DISCOVERY, STRUCTURE, AND SYNTHESIS;1329
23.1.4;RECEPTORS AND THEIR DISTRIBUTION;1329
23.1.5;BIOLOGICAL ACTIONS;1330
23.1.6;CLINICAL APPLICATION OF AM FOR PULMONARY HYPERTENSION;1331
23.1.7;CONCLUSION;1333
23.1.8;References;1333
23.2;178: Endothelin in the Airways;1335
23.2.1;ABSTRACT;1335
23.2.2;INTRODUCTION;1335
23.2.3;SYNTHESIS AND ELIMINATION OF ET-1;1336
23.2.4;ENDOTHELIN RECEPTOR SUBTYPES AND LOCALIZATION;1336
23.2.5;PATHOPHYSIOLOGICAL ROLE;1336
23.2.6;References;1337
23.3;179: PACAP’s Role in Pulmonary Function;1339
23.3.1;ABSTRACT;1339
23.3.2;GENE STRUCTURE AND DISTRIBUTION OF THE PRECURSOR mRNA;1339
23.3.3;RECEPTORS;1339
23.3.4;BIOLOGICAL ACTIONS WITHIN THE LUNG;1340
23.3.5;PATHOPHYSIOLOGICAL IMPLICATIONS;1342
23.3.6;THERAPEUTIC POTENTIAL;1343
23.3.7;References;1344
23.4;180: Tachykinins and Their Receptors in the Lung;1347
23.4.1;ABSTRACT;1347
23.4.2;TACHYKININ RECEPTOR PHARMACOLOGY;1347
23.4.3;TACHYKININ LOCALIZATION IN THE LUNG;1348
23.4.4;TACHYKININ RECEPTOR DISTRIBUTION IN THE LUNG;1348
23.4.5;TACHYKININ-MEDIATED BIOLOGICAL EFFECTS IN THE LUNG;1348
23.4.6;THERAPEUTIC POTENTIAL OF TACHYKININ NK1 RECEPTOR BLOCKADE;1349
23.4.7;THERAPEUTIC POTENTIAL OF TACHYKININ NK2 RECEPTOR BLOCKADE;1349
23.4.8;THERAPEUTIC POTENTIAL OF DUAL TACHYKININ NK1-NK2 RECEPTOR BLOCKADE;1349
23.4.9;THERAPEUTIC POTENTIAL OF BLOCKADE OF THE TACHYKININ NK3 RECEPTOR;1350
23.4.10;CONCLUSION;1350
23.4.11;References;1350
23.5;181: Vasoactive Intestinal Peptide;1353
23.5.1;ABSTRACT;1353
23.5.2;INTRODUCTION: VIP IN THE LUNG;1353
23.5.3;VIP AND ITS FAMILY OF PEPTIDES;1353
23.5.4;DISTRIBUTION AND LOCALIZATION;1353
23.5.5;BIOLOGICAL ACTIONS PERTINENT TO THE LUNG;1354
23.5.6;RECEPTORS;1355
23.5.7;SIGNAL TRANSDUCTION PATHWAYS;1355
23.5.8;PHYSIOLOGICAL ROLES;1355
23.5.9;VIP IN PULMONARY DISEASE;1355
23.5.10;THERAPEUTIC POTENTIAL;1356
23.5.11;References;1357
24;XVII: Opioid Peptides Section;1359
24.1;182: Proenkephalin-Derived Opioid Peptides;1359
24.1.1;ABSTRACT;1359
24.1.2;DISCOVERY OF THE ENKEPHALINS;1359
24.1.3;STRUCTURE OF THE PRECURSOR GENE;1359
24.1.4;DISTRIBUTION OF ENKEPHALIN mRNA AND PEPTIDE;1359
24.1.5;PROCESSING;1360
24.1.6;RECEPTORS;1360
24.1.7;BIOLOGICAL ACTIVITY OF ENKEPHALINS;1361
24.1.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1362
24.1.9;References;1363
24.2;183: Prodynorphin-Derived Opioid Peptides;1365
24.2.1;ABSTRACT;1365
24.2.2;DISCOVERY;1365
24.2.3;STRUCTURE OF THE PRECURSOR mRNA/GENE;1365
24.2.4;PROCESSING;1366
24.2.5;RECEPTORS;1367
24.2.6;CONFORMATIONAL ANALYSIS OF DYN A(1–17);1367
24.2.7;DYNORPHIN EXPRESSION IN THE CENTRAL NERVOUS SYSTEM AND POSSIBLE BIOLOGICAL ACTIONS;1367
24.2.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1368
24.2.9;DRUG ABUSE AND DYNORPHINS;1369
24.2.10;DYNORPHIN EXPRESSION IN PERIPHERAL TISSUES;1369
24.2.11;PERSPECTIVE;1370
24.2.12;References;1370
24.3;184: POMC Opioid Peptides;1371
24.3.1;ABSTRACT;1371
24.3.2;INTRODUCTION;1371
24.3.3;DISCOVERY;1371
24.3.4;DISTRIBUTION;1371
24.3.5;PROCESSING;1372
24.3.6;RECEPTORS;1373
24.3.7;BIOLOGICAL ACTIONS;1374
24.3.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1376
24.3.9;References;1376
24.4;185: Endomorphins as Endogenous Peptides for u-Opioid Receptor: Their Differences in the Pharmacological and Physiological Characters;1379
24.4.1;ABSTRACT;1379
24.4.2;DISCOVERY OF ENDOMORPHINS;1379
24.4.3;DISTRIBUTION OF THE ENDOMORPHIN-2- LIKE IMMUNOREACTIVE NEURONS IN THE CENTRAL NERVOUS SYSTEM;1380
24.4.4;DISTRIBUTION OF THE EM-1-LI NEURONS IN THE CENTRAL NERVOUS SYSTEM;1380
24.4.5;RECEPTOR SELECTIVITY AND ITS MODULATION;1381
24.4.6;BIOLOGICAL ACTIONS OF ENDOMORPHINS;1381
24.4.7;PATHOPHYSIOLOGICAL IMPLICATIONS OF ENDOMORPHINS;1382
24.4.8;CONCLUSION;1383
24.4.9;Acknowledgments;1383
24.4.10;References;1383
24.5;186: Casomorphins and Hemorphins—Opioid Active Peptides Released by Partial Hydrolysis of Structural Proteins;1385
24.5.1;ABSTRACT;1385
24.5.2;DISCOVERY OF THE b-CASOMORPHINS AND THE HEMORPHINS;1385
24.5.3;THE FORMATION OF b-CASOMORPHINS AND HEMORPHINS;1386
24.5.4;RECEPTOR SELECTIVITY AND ITS MODULATION;1387
24.5.5;BIOLOGICAL ACTIONS AND FUNCTIONAL RELEVANCE OF THE b-CASOMORPHINS AND HEMORPHINS;1387
24.5.6;IMPLICATIONS OF b-CASOMORPHINS AND HEMORPHINS IN PATHOPHYSIOLGY;1388
24.5.7;CONCLUSION;1389
24.5.8;Acknowledgments;1389
24.5.9;References;1389
24.6;187: Anti-Opioid Peptides;1391
24.6.1;ABSTRACT;1391
24.6.2;INTRODUCTION;1391
24.6.3;REGULATION OF OPIOID ANALGESIA BY CCK;1391
24.6.4;CCK GENE EXPRESSION IN RESPONSE TO OPIOID ANALGESIA;1392
24.6.5;CCK RELEASE IN RESPONSE TO OPIOID ANALGESIA;1393
24.6.6;CELLULAR AND MOLECULAR MECHANISMS FOR CCK-OPIOID INTERACTIONS;1393
24.6.7;REGULATION OF OPIOID ANALGESIA BY NPFF;1393
24.6.8;REGULATION OF OPIOID ANALGESIA BY NOCICEPTIN;1394
24.6.9;REGULATION OF u-OPIOID SYSTEMS BY MIF-1, TYR-MIF-1, AND TYR-W-MIF-1;1394
24.6.10;Acknowledgment;1395
24.6.11;References;1395
24.7;188: Nociceptin;1397
24.7.1;ABSTRACT;1397
24.7.2;DISCOVERY;1397
24.7.3;STRUCTURE OF PRECURSOR MRNA/GENE;1397
24.7.4;DISTRIBUTION OF MRNA AND PEPTIDE;1399
24.7.5;BIOSYNTHESIS AND DEGRADATION;1400
24.7.6;RECEPTOR;1400
24.7.7;BIOLOGICAL ACTIONS;1400
24.7.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1402
24.7.9;References;1402
24.8;189: Role of Tachykinins in Spinal Nociceptive Mechanisms and Their Interactions with Opioids;1405
24.8.1;ABSTRACT;1405
24.8.2;DISTRIBUTION OF TACHYKININS IN DORSAL ROOT GANGLIA AND THE SPINAL CORD;1405
24.8.3;PLASTICITY OF THE EXPRESSION OF TACHYKININS AND THEIR RECEPTORS FOLLOWING INFLAMMATION AND NERVE INJURY;1405
24.8.4;RELEASE OF TACHYKININS IN THE SPINAL CORD;1406
24.8.5;INVOLVEMENT OF TACHYKININS IN SPINAL NOCICEPTION;1406
24.8.6;NK-1 RECEPTOR AND NEUROPATHIC PAIN;1406
24.8.7;SP-SAPORIN AND NK-1 RECEPTOR EXPRESSING LAMINAE I NEURONS IN NOCICEPTION;1407
24.8.8;INTERACTION BETWEEN TACHYKININS AND OPIOIDS;1407
24.8.9;THE FAILURE OF NK-1 ANTAGONISTS AS ANALGESICS IN HUMANS;1407
24.8.10;References;1408
24.9;190: Exorphin-Opioid Active Peptides of Exogenous Origin;1411
24.9.1;ABSTRACT;1411
24.9.2;OPIOID PEPTIDES DERIVED FROM PLANT PROTEINS;1411
24.9.3;OPIOID PEPTIDES DERIVED FROM ANIMAL PROTEINS;1412
24.9.4;INTRAPROTEIN OPIOID SEQUENCE;1414
24.9.5;CLASSIFICATION OF EXORPHINS ACCORDING TO THEIR STRUCTURE;1414
24.9.6;OPIOID ANTAGONIST AND ANTI-OPIOID PEPTIDE DERIVED FROM PROTEINS;1415
24.9.7;CONCLUSION;1416
24.9.8;Acknowledgments;1416
24.9.9;References;1416
24.10;191: Opioid-Substance P Chimeric Peptides;1419
24.10.1;ABSTRACT;1419
24.10.2;INTRODUCTION;1419
24.10.3;CROSS-INTERACTION OF TACHYKININ AND OPIOID SYSTEMS;1420
24.10.4;TACHYKININ ANTAGONIST–OPIOID AGONIST CHIMERIC COMPOUNDS;1420
24.10.5;TACHYKININ AGONIST–OPIOID AGONIST CHIMERIC COMPOUNDS;1421
24.10.6;CONCLUSION;1423
24.10.7;References;1423
25;XVIII: Neurotrophic Peptides Section;1425
25.1;192: VIP- and PACAP-Related Neuroprotection;1425
25.1.1;ABSTRACT;1425
25.1.2;DISCOVERY;1425
25.1.3;STRUCTURE OF THE PRECURSOR mRNA, DISTRIBUTION, AND PROCESSING;1425
25.1.4;VIP NEUROPROTECTION;1425
25.1.5;RECENT RESEARCH ON VIP: CONCENTRATING ON RECEPTORS AND MECHANISMS;1426
25.1.6;RECENT RESEARCH ON PACAP;1427
25.1.7;NAP: TREATMENT THROUGH A VIP-RELATED MECHANISM;1428
25.1.8;CONCLUSION;1428
25.1.9;Acknowledgments;1428
25.1.10;References;1428
25.2;193: Insulin-Like Growth Factor 1;1431
25.2.1;ABSTRACT;1431
25.2.2;DISCOVERY;1431
25.2.3;STRUCTURE OF PRECURSOR mRNA/GENE;1431
25.2.4;DISTRIBUTION OF THE mRNA;1432
25.2.5;PROCESSING;1433
25.2.6;RECEPTORS;1433
25.2.7;ACTIVE AND/OR SOLUTION CONFORMATION;1434
25.2.8;BIOLOGICAL ACTIONS;1434
25.2.9;PATHOPHYSIOLOGICAL IMPLICATIONS;1435
25.2.10;References;1436
25.3;194: Erythropoietin—A Hematopoietic Hormone with Emerging Diverse Activities;1439
25.3.1;ABSTRACT;1439
25.3.2;DISCOVERY;1439
25.3.3;STRUCTURE OF THE PRECURSOR Epo mRNA/GENE;1439
25.3.4;DISTRIBUTION OF Epo mRNA;1439
25.3.5;PROCESSING OF Epo;1440
25.3.6;THE Epo RECEPTOR;1440
25.3.7;Epo BIOLOGICAL ACTIONS;1440
25.3.8;PATHOPHYSIOLOGICAL IMPLICATIONS;1444
25.3.9;References;1445
25.4;195: Neuregulins;1447
25.4.1;ABSTRACT;1447
25.4.2;DISCOVERY AND STRUCTURE;1447
25.4.3;DISTRIBUTION AND PROCESSING;1447
25.4.4;RECEPTORS;1448
25.4.5;BIOLOGICAL ACTIONS;1449
25.4.6;Acknowledgments;1450
25.4.7;References;1451
25.5;196: The Neurotrophins;1453
25.5.1;ABSTRACT;1453
25.5.2;DISCOVERY OF NERVE GROWTH FACTOR;1453
25.5.3;STRUCTURE OF THE mRNA/GENE;1453
25.5.4;DISTRIBUTION OF THE mRNA;1453
25.5.5;PRECURSOR PROTEIN: PROCESSING AND ACTIVITY;1454
25.5.6;CONFORMATION;1454
25.5.7;RECEPTORS—BINDING SITES;1455
25.5.8;TRKA AND p75 RECEPTORS—STRUCTURE;1455
25.5.9;RECEPTOR SIGNALING;1456
25.5.10;NEUROTROPHINS—RETROGRADE TRANSPORT;1456
25.5.11;p75 RECEPTOR SIGNALING;1457
25.5.12;NEUROTROPHINS—PHYSIOLOGICAL ROLE AND ROLES IN PATHOLOGY;1457
25.5.13;CLINICAL PROSPECTS;1458
25.5.14;References;1458
26;XIX: Blood-Brain Barrier Peptides Section;1461
26.1;197: Amino Acid Transport Across the Blood–Brain Barrier;1461
26.1.1;ABSTRACT;1461
26.1.2;BRAIN AMINO ACID REGULATION;1461
26.1.3;BLOOD–BRAIN BARRIER AMINO ACID TRANSPORT;1462
26.1.4;TRANSPORT SYSTEMS;1462
26.1.5;CONCLUSION;1466
26.1.6;References;1467
26.2;198: Oligopeptide Transport at the Blood–Brain and Blood–CSF Barriers;1469
26.2.1;ABSTRACT;1469
26.2.2;INTRODUCTION;1469
26.2.3;BLOOD–BRAIN BARRIERS: GENERAL PROPERTIES;1469
26.2.4;OLIGOPEPTIDE TRANSPORT AT THE BBB;1470
26.2.5;PEPTIDASES AT THE BBB;1471
26.2.6;OLIGOPEPTIDE TRANSPORTERS AT THE CHOROID PLEXUS;1471
26.2.7;PEPTIDASES AT THE CHOROID PLEXUS;1472
26.2.8;PEPTIDE AND PEPTIDOMIMETIC DRUG TRANSPORT;1472
26.2.9;CONCLUSION;1473
26.2.10;Acknowledgments;1474
26.2.11;References;1474
26.3;199: Opiate Peptides and the Blood–Brain Barrier;1475
26.3.1;ABSTRACT;1475
26.3.2;INTRODUCTION;1475
26.3.3;STABILIZATION;1475
26.3.4;TARGETING;1476
26.3.5;CONCLUSION;1478
26.3.6;References;1478
26.4;200: Permeability of the Blood–Brain Barrier to Neurotrophic Peptides;1481
26.4.1;ABSTRACT;1481
26.4.2;INTRODUCTION;1481
26.4.3;METHODS TO STUDY PERMEATION OF PEPTIDES ACROSS THE BBB: IN VIVO AND IN VITRO MODELS;1481
26.4.4;BINDING PROTEINS THAT AFFECT THE STABILITY AND PERMEATION KINETICS: INTRAVENOUS DELIVERY VERSUS IN SITU BRAIN PERFUSION;1482
26.4.5;PRESENCE OF RECEPTORS AT THE APICAL OR BASOLATERAL SURFACE OF THE BBB: USEFUL OR NOT FOR PEPTIDE TRANSPORT?;1483
26.4.6;ADSORPTIVE ENDOCYTOSIS AND CHEMICAL MODIFICATIONS THAT ENHANCE DELIVERY ACROSS THE BBB;1483
26.4.7;THE INTRACELLULAR TRAFFICKING OF PEPTIDES THAT LEADS TO EXOCYTOSIS;1483
26.4.8;SPECIFIC EXAMPLES OF THE PHARMACOKINETICS OF BBB PERMEATION;1484
26.4.9;THE SITUATION OF THE PARTIALLY DISRUPTED BBB AND SELECTIVE REGULATION OF THE TRANSPORT SYSTEM IN PATHOPHYSIOLOGY;1484
26.4.10;ENHANCED DELIVERY OF NEUROTROPHIC PEPTIDES: HOW IT AFFECTS NEUROREGENERATION;1485
26.4.11;CONCLUSION;1485
26.4.12;Acknowledgment;1485
26.4.13;References;1485
26.5;201: Transport of Basic Peptides at the Blood–Brain Barrier;1489
26.5.1;ABSTRACT;1489
26.5.2;INTRODUCTION;1489
26.5.3;bFGF;1490
26.5.4;TRANSPORT MECHANISM;1492
26.5.5;PEPTIDE DELIVERY TO THE BRAIN VIA ADSORPTIVE-MEDIATED TRANSPORT;1492
26.5.6;CONCLUSION;1492
26.5.7;Acknowledgments;1492
26.5.8;References;1493
26.6;202: Fibroblast Growth Factor and the Blood–Brain Barrier;1495
26.6.1;ABSTRACT;1495
26.6.2;INTRODUCTION;1495
26.6.3;FGF-INDUCED PROTECTION OF CEREBRAL ENDOTHELIUM AND NEURONS;1496
26.6.4;FGF1 AND FGF2 TRANSPORT ACROSS THE BLOOD–BRAIN BARRIER;1496
26.6.5;FGF SECRETION BY MICROVASCULAR ENDOTHELIAL CELLS;1497
26.6.6;FGF MODULATION OF CEREBRAL ENDOTHELIAL CELLS;1497
26.6.7;FGF2 TRANSPORT AND REGULATORY PHENOMENA AT THE CHOROID PLEXUS;1497
26.6.8;THE CSF-EPENDYMAL-BRAIN INTERFACE;1498
26.6.9;MODELING OF PEPTIDE REGULATORY SYSTEMS: INTEGRATING MULTIPLE LIGANDS AND TRANSPORT INTERFACES;1498
26.6.10;CONCLUSION;1499
26.6.11;References;1499
26.7;203: Ingestive Peptides and the Blood–Brain Barrier;1501
26.7.1;ABSTRACT;1501
26.7.2;INTRODUCTION;1501
26.7.3;INSULIN;1501
26.7.4;LEPTIN;1502
26.7.5;GHRELIN;1503
26.7.6;OTHER INGESTIVE PEPTIDES AND PROTEINS: SPECIAL INTERACTIONS WITH THE BBB;1503
26.7.7;CONCLUSION;1504
26.7.8;References;1505
26.8;204: Functional Aspects of Vasoactive Peptides at the Blood–Brain Barrier;1507
26.8.1;ABSTRACT;1507
26.8.2;ANGIOTENSIN;1507
26.8.3;BRADYKININ;1508
26.8.4;INTERPLAY BETWEEN ANGIOTENSIN AND BRADYKININ;1509
26.8.5;SUBSTANCE P;1509
26.8.6;ATRIAL NATRIURETIC PEPTIDE;1510
26.8.7;ENDOTHELINS;1510
26.8.8;ADRENOMEDULLIN;1511
26.8.9;MISCELLANEOUS PEPTIDES WITH VASOACTIVE PROPERTIES IN THE CNS;1511
26.8.10;References;1512
26.9;205: Hypothalamic Neuropeptides and the Blood–Brain Barrier;1515
26.9.1;ABSTRACT;1515
26.9.2;INTRODUCTION;1515
26.9.3;THE CIRCUMVENTRICULAR ORGANS;1515
26.9.4;TRH;1516
26.9.5;GnRH;1516
26.9.6;CORTICOTROPIN-RELEASING HORMONE;1517
26.9.7;VASOPRESSIN (ANTIDIURETIC HORMONE);1517
26.9.8;OXYTOCIN;1518
26.9.9;SOMATOSTATIN;1518
26.9.10;PACAP;1518
26.9.11;References;1518
26.10;206: Diseases Mediated by the BBB: From Alzheimer’s to Obesity;1521
26.10.1;ABSTRACT;1521
26.10.2;INTRODUCTION;1521
26.10.3;LEPTIN AND OBESITY;1521
26.10.4;AMYLOID b PROTEIN EFFLUX AND ALZHEIMER’S DISEASE;1522
26.10.5;METHIONINE ENKEPHALIN AND ALCOHOL WITHDRAWAL;1523
26.10.6;GLUT-1 DEFICIENCY SYNDROME;1523
26.10.7;INSULIN RESISTANCE IN SEPSIS;1524
26.10.8;CONCLUSION;1524
26.10.9;References;1524
27;XX: Other Peptide Topics;1527
27.1;207: Prebiotic Peptides;1527
27.1.1;ABSTRACT;1527
27.1.2;INTRODUCTION;1527
27.1.3;THE PRIMITIVE EARTH SCENARIO;1527
27.1.4;THE FORMATION OF AMINO ACIDS;1528
27.1.5;THE FORMATION OF PEPTIDES;1528
27.1.6;A PEPTIDE WORLD AS THE ORIGIN OF LIFE?;1530
27.1.7;References;1531
27.2;208: Mixture-Based Combinatorial Libraries;1533
27.2.1;ABSTRACT;1533
27.2.2;INTRODUCTION;1533
27.2.3;GENERAL METHODS;1533
27.2.4;m-RECEPTOR LIGANDS;1535
27.2.5;d-RECEPTOR LIGANDS;1536
27.2.6;k-RECEPTOR LIGANDS;1536
27.2.7;m-, d-, AND k-LIGANDS;1536
27.2.8;ORPHAN RECEPTOR LIGANDS;1536
27.2.9;TESTING MIXTURES IN VIVO;1537
27.2.10;CONCLUSION;1537
27.2.11;FUTURE STUDIES;1538
27.2.12;References;1538
27.3;209: Use of Synthetic Peptides for Structural and Functional Analyses of Viruses Like HIV;1541
27.3.1;ABSTRACT;1541
27.3.2;INTRODUCTION;1541
27.3.3;HIV-1-DERIVED SYNTHETIC PEPTIDES;1541
27.3.4;THE HIV-1-SPECIFIC VIRUS PROTEIN U;1542
27.3.5;STRUCTURE AND FUNCTION OF THE LENTIVIRAL PROTEIN R;1543
27.3.6;THE TRANS-ACTIVATOR OF TRANSCRIPTION (Tat) OF HIV-1;1544
27.3.7;THE HIV-1 PROTEASE;1545
27.3.8;THE HIV-1 p6 Gag PROTEIN;1546
27.3.9;THE HIV-1 Gag PROTEINS NC AND MA;1547
27.3.10;CONCLUSION;1547
27.3.11;Acknowledgments;1548
27.3.12;References;1548
27.4;210: Pheromone Peptides;1551
27.4.1;ABSTRACT;1551
27.4.2;INTRODUCTION;1551
27.4.3;BACTERIAL PHEROMONE PEPTIDES;1552
27.4.4;FUNGAL PHEROMONE PEPTIDES;1552
27.4.5;ARTHROPOD PHEROMONE PEPTIDES;1555
27.4.6;ANNELID PHEROMONE PEPTIDES;1556
27.4.7;MOLLUSK PHEROMONE PEPTIDES;1556
27.4.8;VERTEBRATE PHEROMONE PEPTIDES;1556
27.4.9;CONCLUSION;1557
27.4.10;References;1557
27.5;211: Fish Peptides;1561
27.5.1;ABSTRACT;1561
27.5.2;INTRODUCTION;1561
27.5.3;MELANIN-CONCENTRATING HORMONE;1561
27.5.4;UROTENSINS;1562
27.5.5;ADRENOMEDULLIN 2/INTERMEDIN;1562
27.5.6;STANNIOCALCINS;1563
27.5.7;CONCLUSION;1564
27.5.8;References;1564
27.6;212: Peptides and Sleep;1567
27.6.1;ABSTRACT;1567
27.6.2;INTRODUCTION;1567
27.6.3;HYPOTHALAMIC-PITUITARY-SOMATOTROPIC SYSTEM;1567
27.6.4;HYPOTHALAMIC-PITUITARYADRENOCORTICAL SYSTEM;1569
27.6.5;ACTH;1569
27.6.6;HYPOTHALAMIC-PITUITARY-THYROID SYSTEM;1570
27.6.7;OTHER PEPTIDES;1570
27.6.8;CONCLUSION;1571
27.6.9;Acknowledgment;1572
27.6.10;References;1572
27.7;213: Peptide Chronomics;1575
27.7.1;ABSTRACT;1575
27.7.2;PREAMBLE;1575
27.7.3;INTRODUCTION;1575
27.7.4;AVOIDING BLUNDERS;1578
27.7.5;CHRONOMICS SPAWNED BY CHRONOBIOLOGY MAPS DYNAMICS;1581
27.7.6;END POINTS;1581
27.7.7;SUSCEPTIBILITY RHYTHMS;1588
27.7.8;ATLAS;1588
27.7.9;BEGINNINGS OF OPPORTUNISTIC MAPPING ALONG THE SCALE OF YEARS;1588
27.7.10;MAPS OF PEPTIDES IN MEN;1593
27.7.11;PEPTIDE CHRONOMICS IN WOMEN;1593
27.7.12;BREAST CANCER RISK ASSESSMENT;1599
27.7.13;PROSTATE CANCER RISK ASSESSMENT;1599
27.7.14;DISCUSSION;1602
27.7.15;CONCLUSION;1603
27.7.16;Acknowledgments;1607
27.7.17;References;1607
28;Index;1611
29;Color Plates;1643