Handbook of Biologically Active Peptides (eBook)

Front cover 1
Title page 5
Copyright page 6
Table of contents 7
Contributors 21
Preface 41
Foreword 45
I: Plant Peptides Section 47
1: 4-kDa Peptide 47
ABSTRACT 47
DISCOVERY 47
STRUCTURE OF THE PRECURSOR mRNA/GENE 47
DISTRIBUTION OF THE mRNA 47
PROCESSING 48
RECEPTORS 48
ACTIVE AND/OR SOLUTION CONFORMATION 48
BIOLOGICAL ACTIONS 48
References 50
2: AtPep1 Peptides 51
ABSTRACT 51
DISCOVERY 51
STRUCTURE OF AtPep1 AND THE GENE ENCODING THE PRECURSOR PROTEIN ProAtPep1 51
DISTRIBUTION OF ProAtPep1 mRNA 52
PROCESSING OF ProAtPep1 53
AtPep1 RECEPTOR 53
SOLUTION CONFORMATION 53
BIOLOGICAL ACTIONS OF AtPep1 53
Acknowledgments 54
References 54
3: CLAVATA3: A Putative Peptide Ligand Controlling Arabidopsis Stem Cell Specification 55
ABSTRACT 55
DISCOVERY 55
STRUCTURE OF THE PRECURSOR mRNA/GENE 56
RECEPTORS 58
BIOLOGICAL ACTIONS 59
References 60
4: DVL Peptides Are Involved in Plant Development 63
ABSTRACT 63
DISCOVERY 63
STRUCTURE OF THE PRECURSOR mRNA/GENE 64
DISTRIBUTION OF THE DVL1 mRNA 64
PROCESSING 65
RECEPTORS 66
BIOLOGICAL ACTION 66
References 67
5: The POLARIS Peptide 69
ABSTRACT 69
DISCOVERY 69
STRUCTURE OF THE PRECURSOR mRNA/GENE 71
DISTRIBUTION OF THE mRNA 71
PROCESSING 72
BIOLOGICAL ACTIONS 72
References 73
6: Phytosulfokine 75
ABSTRACT 75
INTRODUCTION 75
DISCOVERY AND BIOLOGICAL ACTIONS 75
STRUCTURE OF THE PRECURSOR mRNA/GENE 76
TYROSINE SULFATION 77
RECEPTORS 77
CONCLUSION 77
Acknowledgments 78
References 78
7: RALF Peptides 79
ABSTRACT 79
DISCOVERY 79
STRUCTURE OF THE RALF PEPTIDE AND ITS PRECURSOR cDNA AND GENE 79
DISTRIBUTION OF THE mRNA 80
PROCESSING 80
RECEPTOR 80
SOLUTION CONFORMATION OF RALF 81
BIOLOGICAL ACTION OF RALF 81
Acknowledgment 81
References 82
8: ROTUNDIFOLIA4: A Plant-Specific Small Peptide 83
ABSTRACT 83
DISCOVERY 83
STRUCTURE OF THE PRECURSOR mRNA/GENE 83
DISTRIBUTION OF THE mRNA 84
PROCESSING 84
RECEPTORS 85
BIOLOGICAL ACTIONS 85
References 86
9: The S-Locus Cysteine-Rich Peptide SCR/SP11 87
ABSTRACT 87
DISCOVERY OF SCR 87
STRUCTURE OF THE PRECURSOR mRNA/GENE 89
DISTRIBUTION OF THE mRNA 89
PROCESSING OF THE SCR PROTEIN 90
THE SCR RECEPTOR 90
STRUCTURE 90
BIOLOGICAL ACTIONS 92
References 92
10: Systemins 95
ABSTRACT 95
DISCOVERY OF SYSTEMINS 95
STRUCTURES OF SYSTEMINS AND OF THEIR PRECURSOR cDNAs 96
DISTRIBUTION OF SYSTEMIN SUBFAMILY mRNAs 97
PROCESSING OF THE SYSTEMIN FAMILY PRECURSOR PROTEINS 97
THE LeSys RECEPTOR 98
SOLUTION CONFORMATIONS OF SYSTEMIN SUBFAMILY MEMBERS 98
BIOLOGICAL ACTIONS OF SYSTEMIN FAMILY MEMBERS 98
Acknowledgments 99
References 99
II: Bacterial/Antibiotic Peptides Section 101
11: Cationic Antimicrobial Peptides—The Defensins 101
ABSTRACT 101
DISCOVERY 101
STRUCTURE OF THE PRECURSOR mRNA/GENE 101
DISTRIBUTION AND EXPRESSION OF THE mRNA 102
PROCESSING 104
RECEPTORS 104
ACTIVE CONFORMATION 105
BIOLOGICAL ACTIONS 105
Acknowledgments 111
References 111
12: Cathelicidins: Cationic Host Defense and Antimicrobial Peptides 113
ABSTRACT 113
DISCOVERY 113
STRUCTURE OF THE PRECURSOR mRNA/STRUCTURAL GENE 113
DISTRIBUTION OF CATHELICIDINS 114
PROCESSING 114
RECEPTORS 115
ACTIVE AND/OR SOLUTION CONFORMATION 116
BIOLOGICAL FUNCTIONS 117
Acknowledgments 118
References 118
13: Microcins 121
ABSTRACT 121
DISCOVERY 121
STRUCTURE OF THE PRECURSOR mRNA/STRUCTURAL GENE 121
DISTRIBUTION OF THE mRNA 122
PROCESSING 122
RECEPTORS 124
ACTIVE AND/OR SOLUTION CONFORMATION 124
BIOLOGICAL ACTIONS 125
Acknowledgments 125
References 125
14: Peptaibols 129
ABSTRACT 129
INTRODUCTION 129
CHARACTERISTIC FEATURES OF THE PEPTAIBOLS 129
BIOLOGICAL ORIGINS AND BIOSYNTHESIS OF PEPTAIBOLS 131
PEPTAIBOL STRUCTURES 131
FUNCTIONS AND ACTIVITIES OF PEPTAIBOLS 132
Acknowledgments 133
References 133
15: Nonribosomally Synthesized Microbial Macrocyclic Peptides 135
ABSTRACT 135
STRUCTURAL DIVERSITY OF NRPS SYNTHESIZED PEPTIDES 135
MODULAR STRUCTURE OF NRPSs 136
MACROCYCLIZATION 138
STRUCTURE OF THE SURFACTIN THIOESTERASE DOMAIN 138
BIOCHEMICAL CHARACTERIZATION OF EXCISED THIOESTERASE DOMAINS 139
CHEMOENZYMATIC APPROACHES TOWARD NOVEL CYCLOPEPTIDES 140
THE COMBINATORIAL POTENTIAL OF TE DOMAINS TO SYNTHESIZE CYCLIC PEPTIDE LIBRARIES 141
Acknowledgments 141
References 141
16: Lantibiotics 143
ABSTRACT 143
DISCOVERY 143
STRUCTURE OF THE PRECURSOR mRNA/GENE 143
DISTRIBUTION OF THE mRNA 143
PROCESSING 144
RECEPTORS 144
ACTIVE AND/OR SOLUTION CONFORMATION 144
BIOLOGICAL ACTIONS 146
Acknowledgments 149
References 149
17: The Nonlantibiotic Heat-Stable Bacteriocins in Gram-Positive Bacteria 153
ABSTRACT 153
DISCOVERY 153
SYNTHESIS 153
BIOLOGICAL ACTIONS AND RECEPTORS 156
STRUCTURE 157
FUTURE TRENDS 158
Acknowledgments 158
References 158
18: Colicins: Bacterial/Antibiotic Peptides 161
ABSTRACT 161
DISCOVERY AND CLASSIFICATION 161
STRUCTURE OF THE PRECURSOR mRNA/GENE 161
THE DOMAIN CONCEPT 162
SEQUENCE COMPARISONS 163
X-RAY STRUCTURES OF COLICINS 166
MECHANISM OF IMPORT ACROSS OUTER MEMBRANE 168
AREAS OF RESEARCH ENCOMPASSED BY COLICIN STUDIES 168
Acknowledgment 168
References 168
III: Fungal/Antifungal Peptides Section 171
19: Fungal Peptides with Antifungal Activity 171
ABSTRACT 171
DISCOVERY 171
STRUCTURE 173
BIOLOGICAL ACTION 174
References 174
20: Toxins from Basidiomycete Fungi (Mushroom): Amatoxins, Phallotoxins, and Virotoxins 177
ABSTRACT 177
INTRODUCTION 177
DISCOVERY OF MUSHROOM TOXINS 177
STRUCTURES OF MUSHROOM TOXINS 179
TOXIC ACTIONS OF MUSHROOM TOXINS 179
Acknowledgments 181
References 181
21: Fungal Peptides with Ribonuclease Activity 183
ABSTRACT 183
DISCOVERY 183
STRUCTURE 183
BIOLOGICAL ACTION 185
References 189
22: Fungal Ribosome Inactivating Proteins 191
ABSTRACT 191
DISCOVERY 191
STRUCTURE 192
BIOLOGICAL ACTIONS 192
Acknowledgments 194
References 194
23: Peptides and Depsipeptides from Plant Pathogenic Fungi 197
ABSTRACT 197
PHYTOTOXINS 197
DEPSIPEPTIDES AND PEPTIDES 198
CONCLUSION 201
References 202
IV: Invertebrate Peptides Section 203
24: Insect Diuretic and Antidiuretic Hormones 203
ABSTRACT 203
DISCOVERY 203
STRUCTURE OF THE PRECURSOR mRNA/GENE 204
DISTRIBUTION OF mRNA AND PEPTIDES 205
PEPTIDE PROCESSING 205
RECEPTORS 205
STRUCTURE-ACTIVITY AND ACTIVE CONFORMATION 206
BIOLOGICAL ACTIONS 206
CONCLUSION 207
References 207
25: Developmental Peptides: ETH, Corazonin, and PTTH 209
ABSTRACT 209
DISCOVERY 209
STRUCTURE OF THE PRECURSOR mRNA/GENE AND PEPTIDE PROCESSING 210
PTTH 211
DISTRIBUTION OF THE mRNA AND PEPTIDES 212
PTTH 212
RECEPTORS 212
ACTIVE AND/OR SOLUTION CONFORMATION 213
BIOLOGICAL ACTIONS 213
PTTH 214
References 214
26: Tachykinins and Tachykinin-Related Peptides in Invertebrates 217
ABSTRACT 217
DISCOVERY 217
STRUCTURE OF THE PRECURSOR mRNA/GENE 218
DISTRIBUTION OF mRNA AND PEPTIDES 219
PEPTIDE PROCESSING 220
RECEPTORS OF TKRPs 220
STRUCTURE-ACTIVITY AND ACTIVE CONFORMATION 221
BIOLOGICAL ACTIONS 221
CONCLUSION 221
References 222
27: Proctolin in Insects 223
ABSTRACT 223
DISCOVERY 223
STRUCTURE OF THE PRECURSOR mRNA/GENE 223
DISTRIBUTION OF mRNA 223
PROCESSING 224
RECEPTORS 225
STRUCTURE—ACTIVITY AND ACTIVE CONFORMATION 225
BIOLOGICAL ACTIONS 226
References 227
28: Sulfakinins 229
ABSTRACT 229
DISCOVERY 229
STRUCTURE OF THE PRECURSOR mRNA/GENE 229
PROCESSING 230
TISSUE DISTRIBUTION 230
RECEPTORS 231
STRUCTURE/CONFORMATION-ACTIVITY RELATIONSHIPS 231
BIOLOGICAL ACTIONS 232
References 232
29: The Invertebrate AKH/RPCH Family 235
ABSTRACT 235
DISCOVERY 235
PEPTIDE AND PRECURSOR STRUCTURE AND PROCESSING 235
DISTRIBUTION 236
SOLUTION CONFORMATION OF AKH AND RECEPTORS FOR AKH 236
BIOLOGICAL ACTIONS 237
Acknowledgments 238
References 238
30: Insect Myosuppressins/FMRFamides and FL/IRFamides/NPFs 239
ABSTRACT 239
DISCOVERY 239
STRUCTURE OF THE PRECURSOR mRNA/GENE 240
DISTRIBUTION OF mRNA 241
PROCESSING 242
RECEPTORS 242
STRUCTURE–ACTIVITY AND ACTIVE CONFORMATION 243
BIOLOGICAL ACTION 244
References 245
31: Allatostatins in the Insects 247
ABSTRACT 247
DISCOVERY 247
STRUCTURE OF ALLATOSTATIN PRECURSORS 247
DISTRIBUTION OF mRNA AND PEPTIDES 248
PEPTIDE PROCESSING 249
ALLATOSTATIN RECEPTORS 249
STRUCTURE–ACTIVITY AND ACTIVE CONFORMATIONS 250
BIOLOGICAL ACTIONS 251
CONCLUSION 251
References 251
32: The FXPRLamide (Pyrokinin/PBAN) Peptide Family 253
ABSTRACT 253
DISCOVERY 253
STRUCTURE OF THE PRECURSOR mRNA/GENE 253
DISTRIBUTION OF mRNA AND PEPTIDES 254
PEPTIDE PROCESSING 255
RECEPTORS OF IXPRLamides 256
STRUCTURE–ACTIVITY RELATIONSHIPS AND ACTIVE CONFORMATION 256
BIOLOGICAL ACTIONS 257
References 257
33: Insect Pigment Dispersing Factor and Bursicon 259
ABSTRACT 259
INSECT PIGMENT DISPERSING FACTOR 259
BURSICON 261
References 265
34: Crustacean Bioactive Peptides 267
ABSTRACT 267
INTRODUCTION 267
PROCTOLIN 267
CRUSTACEAN CARDIOACTIVE PEPTIDE 267
SULFAKININS 270
NEUROPEPTIDE F 270
OPIOID–ENKEPHALIN 270
ORCOKININ AND ORCOMYOTROPIN 271
ALLATOSTATIN 271
TACHYKININ-RELATED PEPTIDES 272
KININS 272
PYROKININ/PBAN 272
SIFAMIDE 272
MISCELLANEOUS 273
References 273
35: Crustacean Chromatophorotrophins and Hyperglycemic Hormone Peptide Families 275
ABSTRACT 275
INTRODUCTION 275
CHROMATOPHOROTROPHIC HORMONES 275
CRUSTACEAN HYPERGLYCEMIC HORMONES 276
References 279
36: Molluscan Bioactive Peptides 281
ABSTRACT 281
FMRFamide, FMRFamide-RELATED PEPTIDES (FaRPs) 281
PEPTIDES AND METABOLISM: ENERGY FLOW AND GROWTH 282
PEPTIDES AND FEEDING BEHAVIOR 283
PEPTIDES AND RENAL FUNCTION 284
TACHYKININS 284
References 285
37: Molluscan Peptides and Reproduction 287
ABSTRACT 287
PEPTIDES AND REPRODUCTION 287
DISCOVERY 289
VP/OT: DISCOVERY 289
PHEROMONES: DISCOVERY 290
References 291
38: Free-Living Nematode Peptides 293
ABSTRACT 293
INTRODUCTION 293
FMRFamide-LIKE PEPTIDES (FLPs) 293
NEUROPEPTIDE-LIKE PEPTIDES (NLPs) 296
INSULINS (INSs) 296
ANTIMICROBIAL PEPTIDES 298
Acknowledgment 299
References 299
39: Parasitic Nematode Peptides 301
ABSTRACT 301
INTRODUCTION 301
FMRFamide-LIKE PEPTIDES (FLPs) 301
TKQELE 305
References 305
V: Amphibian Peptides Section 307
40: Amphibian Tachykinins 307
ABSTRACT 307
DISCOVERY 307
STRUCTURE OF THE PRECURSOR mRNA/GENE 308
AMPHIBIAN TK DISTRIBUTION 309
RECEPTORS 310
ACTIVE AND/OR SOLUTION CONFORMATION 310
BIOLOGICAL ACTIONS 310
PATHOLOGICAL IMPLICATIONS 313
References 313
41: Opioid Peptides from Frog Skin and Bv8-Related Peptides 315
ABSTRACT 315
OPIOID PEPTIDES 315
A BRIEF HISTORY 315
STRUCTURE AND CONFORMATION 316
BIOLOGICAL ACTIONS 317
Bv8/PROKINETICIN FAMILY (SWISS-PROT: Q9PW66) 318
References 320
42: Amphibian Bombesin-like Peptides 323
ABSTRACT 323
INTRODUCTION 323
AMPHIBIAN BOMBESINS 323
AMPHIBIAN PHYLLOLITORINS 325
RANATENSIN-LIKE PEPTIDES 325
GASTRIN-RELEASING PEPTIDE 326
PHYLOGENETIC CONSIDERATIONS AND IMPLICATIONS FOR ADDITIONAL MAMMALIAN BOMBESIN-LIKE PEPTIDES 326
References 327
43: Host Defense Peptides from Australian Amphibians: Caerulein and Other Neuropeptides 329
ABSTRACT 329
INTRODUCTION 329
THE CAERULEIN PEPTIDES 329
PEPTIDES RELATED TO CAERULEIN 331
TRYPTOPHYLLIN PEPTIDES 332
DISULFIDE NEUROPEPTIDES FROM THE GENUS CRINIA 333
Acknowledgments 333
References 333
44: Bradykinin-Related Peptides from Frog Skin 337
ABSTRACT 337
DISCOVERY AND DISTRIBUTION 337
BIOSYNTHESIS OF BRADYKININ AND RELATED PEPTIDES 337
MOLECULAR VARIANTS OF BK 338
BIOLOGICAL ACTIVITIES 339
References 340
45: The Dermaseptins 341
ABSTRACT 341
THE DERMASEPTIN SUPERFAMILY 341
THE PREPRODERMASEPTINS 343
ACTIVITIES OF THE PREPRODERMASEPTINDERIVED PEPTIDES 346
STRUCTURAL FEATURES AND MECHANISMS OF MICROBICIDAL ACTIVITY 347
References 349
46: The Temporins 351
ABSTRACT 351
DISCOVERY 351
BIOSYNTHESIS OF THE TEMPORINS 352
MOLECULAR HETEROGENEITY OF THE TEMPORINS 353
BIOLOGICAL ACTIVITIES OF THE TEMPORINS 353
POTENTIAL CLINICAL AND COMMERCIAL APPLICATIONS 354
References 354
47: Chromogranins/Secretogranins and Derived Peptides: Insights from the Amphibian Model 357
ABSTRACT 357
DISCOVERY 357
STRUCTURE OF THE PRECURSOR mRNA/GENE 357
DISTRIBUTION OF THE mRNA 360
BIOLOGICAL ACTIONS 362
Acknowledgments 364
References 364
48: Sodefrin and Related Pheromones 367
ABSTRACT 367
DISCOVERY 367
STRUCTURE OF THE PRECURSOR mRNA/GENE 368
DISTRIBUTION OF THE mRNA 369
PROCESSING OF THE PRECURSORS 369
RECEPTORS 369
STRUCTURE–ACTIVITY RELATIONSHIPS 371
BIOLOGICAL ACTIONS 371
PHYSIOLOGICAL IMPLICATION 372
References 372
49: Amphibian Neurohypophysial Peptides 373
ABSTRACT 373
DISCOVERY 373
STRUCTURE OF THE PRECURSOR mRNA/GENE 373
DISTRIBUTION OF AVT AND MT 374
RECEPTOR STRUCTURE AND DISTRIBUTION 374
MAJOR BIOLOGICAL ACTIONS OF AVT AND MT 374
STRUCTURE AND FUNCTION OF HYDRINS 375
References 376
50: Bombinins 379
ABSTRACT 379
DISCOVERY 379
SOLUTION CONFORMATION 381
STRUCTURE OF THE PRECURSOR mRNA/GENE 381
BIOLOGICAL ACTIVITY 381
MODE OF ACTION STUDIES 382
Acknowledgments 383
References 383
VI: Venom Peptides Section 385
51: Scorpion Venom Peptides 385
INTRODUCTION 385
DISCOVERY AND DOCUMENTED BIODIVERSITY 385
THREE-DIMENSIONAL FOLDING 386
SCORPION TOXIN PRECURSORS 387
RECEPTOR SITES 387
MOLECULAR BASIS OF THEIR ACTIVITY 387
CONCLUSION 389
Acknowledgments 389
References 389
52: Snake Venom Peptides 401
ABSTRACT 401
INTRODUCTION 401
THREE-FINGER TOXINS 401
PROTEASE INHIBITOR HOMOLOGS 404
CROTAMINE-LIKE MYOTOXINS 405
SARAFOTOXINS 405
CRISP FAMILY TOXINS 405
NATRIURETIC PEPTIDES 405
DISINTEGRINS 406
C-TYPE LECTINS AND LECTIN-LIKE PROTEINS 406
WAGLERINS 406
BRADYKININ-POTENTIATING PEPTIDES 406
AVIT PEPTIDES 407
MISCELLANEOUS PEPTIDES 407
References 408
53: Sea Anemone Venom Peptides 409
ABSTRACT 409
INTRODUCTION 409
ION CHANNEL BLOCKERS AND MODULATORS 409
CYTOLYSINS 411
OTHER BIOACTIVE PEPTIDES 412
Acknowledgments 412
References 412
54: Spider Venom Peptides 415
ABSTRACT 415
INTRODUCTION 415
METHODOLOGICAL APPROACHES IN THE ISOLATION OF NOVEL SPIDER VENOM PEPTIDES 415
STRUCTURE OF THE PRECURSOR SPIDER VENOM PEPTIDE AND POSTTRANSLATIONAL PROCESSING 416
STRUCTURAL ORGANIZATION OF SPIDER VENOM PEPTIDES: VARIATIONS ON AN ANCESTRAL FOLD 416
SPIDER PEPTIDE TOXINS MODULATING Nav CHANNEL FUNCTION: BLOCKERS AND GATING MODIFIERS 416
SPIDER PEPTIDE TOXINS MODULATING VOLTAGE-GATED POTASSIUM CHANNELS 420
SPIDER PEPTIDE TOXINS MODULATING ON Cav CHANNELS 421
SPIDER PEPTIDE TOXINS ACTING ON ACID-SENSING ION CHANNELS 422
SPIDER PEPTIDE TOXINS WITH NONSELECTIVE ACTIONS ON VOLTAGE-GATED ION CHANNELS: PROMISCUOUS TOXINS 422
SPIDER PEPTIDE TOXINS ACTING ON MECHANOSENSITIVE ION CHANNELS 422
SPIDER TOXINS ACTING ON GLUTAMATE RECEPTORS OR TRANSPORTERS 422
SPIDER TOXINS ACTING ON NEUROTRANSMITTER RELEASE (PRESYNAPTIC TOXINS) 423
SPHINGOMYELINASES D TOXINS FROM SPIDER VENOMS 423
ANTIMICROBIAL AND CYTOLYTIC PEPTIDE TOXINS FROM SPIDER VENOM 424
CONCLUSION 425
References 425
55: Conus Snail Venom Peptides 427
ABSTRACT 427
INTRODUCTION: THE BIODIVERSITY OF VENOMOUS MOLLUSCS 427
DISCOVERY OF CONOTOXINS 427
PRECURSOR STRUCTURE, EXPRESSION, AND PROCESSING: CONOTOXIN SUPERFAMILIES 428
DEFINITION OF CONOTOXIN FAMILIES, RECEPTOR TARGETS, STRUCTURES 430
BIOLOGICAL MECHANISMS, THERAPEUTIC APPLICATIONS 432
Acknowledgments 433
References 433
56: Insect Venom Peptides 435
ABSTRACT 435
INTRODUCTION 435
PEPTIDES FROM THE VENOMS OF SOCIAL HYMENOPTERA 436
PEPTIDE TOXINS FROM SOCIAL WASPS 437
PEPTIDES FROM THE VENOMS OF SOLITARY WASPS 438
PEPTIDES FROM ANT VENOMS 439
Aknowledgments 440
References 440
57: Worm Venom Peptides 443
ABSTRACT 443
INTRODUCTION 443
NEMERTINE PEPTIDE NEUROTOXINS 444
NEMERTINE PEPTIDE CYTOLYSINS 445
ANNELID (GLYCERA) NEUROTOXIN 445
PEPTIDE CYTOLYSINS FROM OTHER WORM PHYLA 446
CONCLUSION 446
References 446
58: Targets and Therapeutic Properties of Venom Peptides 449
ABSTRACT 449
ANTICOAGULANTS AND THROMBOLYTIC AGENTS 449
ANTIHYPERTENSIVE AGENTS 456
ANTIARRHYTHMIC AGENTS 456
CONGESTIVE HEART FAILURE 456
ANTIMICROBIAL PEPTIDES 456
IMMUNOMODULATORY PEPTIDES 457
ANTITUMOR PEPTIDES 457
ANALGESIA 458
DIABETES MELLITUS 458
Acknowledgments 458
References 458
59: Structure-Function Strategies to Improve the Pharmacological Value of Animal Toxins 461
ABSTRACT 461
CHEMICAL SYNTHESIS VERSUS GENETIC ENGINEERING 461
PEPTIDE IMPROVEMENT 461
DESIGN OF NOVEL PEPTIDE ANALOGS 462
BENEFITS OF SIZE REDUCTION IN PEPTIDES 462
RELEVANCE OF CHIMERA AND LABELING APPROACHES 462
STRATEGIES IMPLYING A CHANGE IN THE PATTERN OF HALF-CYSTINE PAIRS 463
WHAT ABOUT THE DIPOLE MOMENT OF VENOM PEPTIDES? 464
FUNCTIONAL DERIVATION OF VENOM PEPTIDES 464
IMPROVING PEPTIDE STABILITY 464
CONCLUSION 465
References 465
VII: Cancer/Anticancer Peptides Section 467
60: Analogs of Luteinizing Hormone-Releasing Hormone (LHRH) in Cancer 467
ABSTRACT 467
INTRODUCTION 467
ANTAGONISTS OF LHRH 468
RECEPTORS FOR LHRH ON TUMORS 468
CYTOTOXIC LHRH ANALOGS 469
EFFECTS OF ANALOGS OF LHRH ON TUMORS 469
CYTOTOXIC ANALOGS OF LHRH 469
SIDE EFFECTS OF CYTOTOXIC LHRH ANALOGS 471
CONCLUSION 472
References 472
61: Bombesin-Related Peptides and Neurotensin: Effects on Cancer Growth/Proliferation and Cellular Signaling in Cancer 475
ABSTRACT 475
INTRODUCTION 475
BN-RELATED PEPTIDES (GRP, NMB) 475
NEUROTENSIN (NT) 477
References 478
62: Somatostatin and NPY 481
ABSTRACT 481
INTRODUCTION 481
SOMATOSTATIN 481
NPY 484
References 486
63: Bradykinin and Cancer 489
ABSTRACT 489
INTRODUCTION 489
KININ CHEMISTRY AND BIOLOGY 489
BRADYKININ ANTAGONISTS 490
BRADYKININ AND CANCER 491
References 492
64: Endothelin 493
ABSTRACT 493
ENDOTHELIN-1 493
ET-1 ASSOCIATED SIGNAL TRANSDUCTION PATHWAYS 493
ENDOTHELIN EXPRESSION IN CANCER 493
ENDOTHELIN RECEPTOR EXPRESSION IN CANCER 494
ENDOTHELIN AS A MITOGEN 495
ENDOTHELIN AND APOPTOSIS 495
ENDOTHELIN AND ANGIOGENESIS 495
ENDOTHELIN-1 AND TUMOR PROGRESSION/METASTASES 496
ENDOTHELIN ANTAGONISM IN VIVO 496
CLINICAL TRIALS 496
References 496
65: Adrenomedullin: An Esoteric Juggernaut of Human Cancers 499
ABSTRACT 499
INTRODUCTION 499
AM EXPRESSION 499
GROWTH REGULATION 500
ANTIAPOPTOSIS 500
MIGRATION/INVASION 501
ANGIOGENESIS 501
IMMUNE REGULATION 501
THERAPEUTIC STRATEGIES AND CONCLUSION 502
References 502
66: Angiotensin Peptides and Cancer 505
ABSTRACT 505
INTRODUCTION 505
ACE AND AT1 RECEPTOR POLYMORPHISMS AND CANCER 506
EFFECTS OF ACE INHIBITORS AND ARBs ON CANCER CELL GROWTH AND TUMORIGENESIS 506
MECHANISMS OF ACTION OF ANG II 507
INHIBITION OF HUMAN CANCER CELL GROWTH BY ANG-(1-7) 508
CONCLUSION 509
References 509
67: Gastrin and Cancer 513
ABSTRACT 513
INTRODUCTION 513
EXPRESSION OF GASTRINS IN NORMAL TISSUE 513
THE GASTRIN RECEPTOR(S) 514
EXPRESSION OF GASTRIN IN TUMORS 514
GASTRIN AS A TUMOR GROWTH FACTOR 515
CONCLUSION 515
References 516
68: VIP and PACAP as Autocrine Growth Factors in Breast and Lung Cancer 519
ABSTRACT 519
INTRODUCTION 519
VIP/PACAP PEPTIDES 519
VIP RECEPTORS 520
SECOND MESSENGERS 520
PROLIFERATION 521
TUMOR IMAGING 521
CONCLUSION 521
References 522
69: Oxytocin and Cancer 525
ABSTRACT 525
MOVING FROM PHYSIOLOGY TO NEOPLASTIC PATHOLOGY 525
OT AS A MODULATOR OF CELL GROWTH IN OTR-EXPRESSING TUMORS 526
THE OT/OTR SYSTEM AND CANCER 527
References 527
70: Antagonists of Growth Hormone–Releasing Hormone (GHRH) in Cancer 529
ABSTRACT 529
INTRODUCTION 529
THERAPEUTIC INDICATIONS OF GHRH ANTAGONISTS 530
ANTAGONISTIC ANALOGS OF GHRH 530
GHRH AND GHRH RECEPTORS IN HUMAN CANCERS 531
MECHANISMS OF TUMOR INHIBITION BY GHRH ANTAGONISTS 532
INHIBITORY EFFECTS OF GHRH ANTAGONISTS ON HUMAN EXPERIMENTAL CANCERS IN VIVO 532
CONCLUSION 533
References 534
VIII: Vaccine Peptides Section 537
71: Cancer Immunotherapy with Rationally Designed Synthetic Peptides 537
ABSTRACT 537
CANCER IMMUNOTHERAPY 537
CURRENT VACCINATION STRATEGIES 538
ACTIVE IMMUNOTHERAPEUTIC STRATEGIES USING PEPTIDES 539
IDENTIFICATION OF T AND B CELL EPITOPES 540
RATIONAL DESIGN OF PEPTIDE VACCINES 541
ANTITUMOR IMMUNITY WITH PEPTIDE VACCINES 542
CONCLUSION 542
References 543
72: Peptide Vaccines for Cancer Treatment 545
ABSTRACT 545
USING THE IMMUNE SYSTEM TO TREAT CANCER 545
IDENTIFICATION OF TUMOR ANTIGENS AND PEPTIDES USING ENDOGENOUS IMMUNITY PRESENT IN CANCER PATIENTS 546
COMMON TUMOR ANTIGENS AND ANTIGENIC PEPTIDES RECOGNIZED BY T CELLS 546
FEATURES OF TUMOR-SPECIFIC T CELLS 548
CLINICAL TRIALS OF PEPTIDE BASED CANCER VACCINES 548
STRATEGIES FOR ENHANCING THE EFFICACY OF PEPTIDE-BASED VACCINES 549
CONCLUSION 550
Acknowledgments 550
References 550
73: Antiadhesin Synthetic Peptide Consensus Sequence Vaccine and Antibody Therapeutic for Pseudomonas Aeruginosa 553
ABSTRACT 553
DISEASE TARGET 553
BACKGROUND AND AVAILABLE THERAPIES 553
WHY PEPTIDES 554
CONTRIBUTIONS 556
FUTURE OUTLOOK 559
CONCLUSION 559
References 560
74: Peptide Vaccines for Malaria 561
ABSTRACT 561
INTRODUCTION 561
MALARIAL VACCINES 562
MAIN MALARIAL ANTIGENS INVOLVED IN TARGET CELL BINDING 563
VACCINE DESIGN BASED ON A STRUCTURAL-FUNCTION RELATIONSHIP 564
DESIGN BASED ON THE MHC-PEPTIDE-TCR COMPLEX CONFORMATION 566
DESIGN BASED ON STRUCTURALLY MODIFIED ANTIGEN BINDING TO HLADRb1* MOLECULES 567
DESIGN BASED ON MALARIAL ANTIGENS’ STRUCTURAL MODIFICATION BY INTRODUCING PEPTIDE BOND ISOSTERS 568
CONCLUSION 570
Acknowledgments 570
References 570
75: Peptide Vaccine for Otitis Media 573
ABSTRACT 573
DISEASE TARGET 573
BACKGROUND OF AVAILABLE THERAPIES 573
WHY PEPTIDES? 574
OUR CONTRIBUTIONS TO THE AREA 577
FUTURE OUTLOOK 578
References 578
76: Peptide Vaccine for Alzheimer’s Disease 581
ABSTRACT 581
INTRODUCTION 581
IN VITRO MODULATION OF b-AMYLOID FORMATION 581
EFRH PHAGE ELICITS ANTIBODIES AGAINST b-AMYLOID PEPTIDE 582
PEPTIDES AS VACCINES FOR PREVENTION AND/OR REDUCTION OF AMYLOID PLAQUES IN AD TRANSGENIC MICE 583
ACTIVE IMMUNIZATION OF hAPP TRANSGENIC MICE WITH EFRH-PHAGE AS PEPTIDE VACCINE 584
FUTURE OUTLOOK 585
Acknowledgments 585
References 585
77: Peptide Dendrimers as Immunogens 587
ABSTRACT 587
INTRODUCTION 587
BACKGROUND AND DISCOVERY 587
DESIGN OF PEPTIDE DENDRIMERS AS IMMUNOGENS 588
IMMUNOLOGICAL PROPERTY OF MAPs 589
CELL-MEDIATED RESPONSES INDUCED BY LIPIDATED MAPs 589
REASONS FOR INCREASED IMMUNOGENICITY 590
SYNTHESIS 590
CONTRIBUTION AND FUTURE OUTLOOK 591
References 592
IX: Immunological and Inflammatory Peptides Section 593
78: Chemotactic Peptide Ligands for Formylpeptide Receptors Influencing Inflammation 593
ABSTRACT 593
BACKGROUND 593
FORMYLPEPTIDE RECEPTORS 593
AGONIST PEPTIDES OF FPRs 594
MAMMALIAN PEPTIDES 595
PERSPECTIVES 597
Acknowledgments 597
References 597
79: Complement-Derived Inflammatory Peptides: Anaphylatoxins 599
ABSTRACT 599
HISTORICAL PERSPECTIVE AND SCOPE 599
PRECURSOR mRNA/GENE STRUCTURE, EXPRESSION, AND REGULATION OF ANAPHYLATOXINS 599
GENERATION OF C3a AND C5a ANAPHYLATOXINS 600
STRUCTURE OF ANAPHYLATOXINS 601
RECEPTORS FOR ANAPHYLATOXINS 602
BIOLOGICAL ACTIONS OF ANAPHYLATOXINS 602
PATHOPHYSIOLOGICAL IMPLICATIONS OF ANAPHYLATOXINS 603
Acknowledgment 603
References 603
80: Chemokines: A New Peptide Family of Neuromodulators 605
ABSTRACT 605
DISCOVERY 606
STRUCTURE OF THE PRECURSOR mRNA/GENE 606
DISTRIBUTION OF SDF-1 mRNA AND PROTEIN 606
PROCESSING OF THE PRECURSOR 608
RECEPTORS AND SIGNALING CASCADES 608
RECEPTOR EXPRESSION AND DISTRIBUTION 608
CONFORMATION 609
BIOLOGICAL ACTIONS 609
PATHOPHYSIOLOGICAL IMPLICATIONS 610
References 610
81: Immune Peptides Related to Dipeptidyl Aminopeptidase IV/CD26 613
ABSTRACT 613
INTRODUCTION 613
DP IV/CD26 IN THE IMMUNE SYSTEM 613
DP IV EFFECTOR PEPTIDES 614
PRIMARY DP IV EFFECTOR PEPTIDES 615
SECONDARY IMMUNORELEVANT DP IV PEPTIDE SUBSTRATES 616
PEPTIDE INHIBITORS OF DP IV 617
References 617
82: RGD-Peptides and Some Immunological Problems 619
ABSTRACT 619
DISCOVERY OF THE ANTIADHESIVE RGD-PEPTIDES 619
RGD-PEPTIDES IN PLATELET AGGREGATION 620
BIOLOGICALLY ACTIVE CONFORMATION OF RGD-PEPTIDES 621
RGD PEPTIDES IN IMMUNOLOGICAL PHENOMENA 621
RGD-PEPTIDES AND PATHOGEN INVASIONS 622
RGD-PEPTIDES IN OTHER PATHOLOGICAL PHENOMENA 622
RGD RETROSEQUENCES IN PROTEINS 623
References 623
83: Neuropeptides That Regulate Immune Responses 625
ABSTRACT 625
Acknowledgment 628
References 628
84: Peptides as Targets of T Cell-Mediated Immune Responses 631
ABSTRACT 631
INTRODUCTION 631
MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I AND CLASS II MOLECULES 632
CHARACTERISTICS OF PEPTIDES PRESENTED BY MHC-CLASS I 633
CHARACTERISTICS OF PEPTIDES PRESENTED BY MHC-CLASS II 634
BIOLOGICAL ROLES OF MHC-BOUND PEPTIDES 635
AUTOIMMUNE DISEASES 636
THERAPEUTIC USE OF PEPTIDES 637
CONCLUSION 638
References 638
85: The Use of Positional Scanning Synthetic Peptide Combinatorial Libraries to Identify Immunological Relevant Peptides 641
ABSTRACT 641
DEFINITION OF POSITIONAL SCANNING SYNTHETIC COMBINATORIAL PEPTIDE LIBRARIES (PS-SCL) 641
USE OF PS-SCL TO DETERMINE ANTIBODY LIGANDS 642
USE OF PS-SCL FOR T CELL EPITOPE MAPPING 644
USE OF PS-SCL TO IDENTIFY MHC BINDING MOTIFS 645
CONCLUSION 646
References 646
86: Copolymer 1 and Related Peptides as Immunomodulating Agents 649
ABSTRACT 649
INTRODUCTION 649
SUPPRESSION OF EAE BY GA 650
OTHER PEPTIDES RELATED TO MS 650
CLINICAL TRIALS WITH COPOLYMER 1 651
MECHANISM OF ACTION OF GLATIRAMER ACETATE 651
IN SITU IMMUNOMODULATION AND NEUROGENRATION IN THE CNS 652
POTENTIAL OF GA FOR THE SUPPRESSION OF OTHER AUTOIMMUNE DISORDERS—STUDIES ON INFLAMMATORY BOWEL DISEASES 653
EFFECT OF COPOLYMER 1 ON GRAFT REJECTION 653
CONCLUSION 654
References 654
87: CLIP—A Multifunctional MHC Class II–Associated Self-Peptide 657
ABSTRACT 657
INTRODUCTION 657
THE CLIP RECEPTORS: MHC CLASS II MOLECULES 657
PROTEOLYSIS OF II AND GENERATION OF CLIP 660
FLANKING RESIDUES AND SELF-RELEASE OF CLIP 661
A CHAPERONE FACILITATING CLIP RELEASE: HLA-DM/H2-DM 661
MEMBRANE MICRODOMAINS 662
CLIP AS AN ANTAGONIST OF TH1 POLARIZATION 663
CONCLUSION 664
References 665
X: Brain Peptides Section 667
88: Vasopressin and Oxytocin 667
ABSTRACT 667
DISCOVERY 667
STRUCTURE OF THE PRECURSOR mRNA/GENE 668
DISTRIBUTION OF THE mRNA 669
PROCESSING OF THE PRECURSOR 670
RECEPTORS 671
ACTIVE AND/OR SOLUTION CONFORMATION 672
BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY 672
PATHOPHYSIOLOGICAL IMPLICATIONS 672
References 673
89: Thyrotrophin-Releasing Hormone: New Functions for an Ancient Peptide 675
ABSTRACT 675
DISCOVERY OF TRH 675
STRUCTURE OF THE PRECURSOR mRNA/GENE 675
DISTRIBUTION OF PRE-PROTRH mRNA AND PRE-PRO-TRH-DERIVED PEPTIDES 676
PROCESSING OF THE TRH PRECURSOR 676
DISTRIBUTION OF TRH RECEPTORS AND THE TRH DEGRADING ENZYME 676
TRH RECEPTOR SIGNALING CASCADES 677
BIOLOGICAL ACTIONS OF TRH WITHIN THE BRAIN AND PITUITARY 677
PATHOPHYSIOLOGICAL IMPLICATIONS 679
References 679
90: Gonadotrophin Releasing Hormone 681
ABSTRACT 681
DISCOVERY AND BACKGROUND 681
STRUCTURE OF GnRHS AND THEIR PRECURSORS 681
GnRH DISTRIBUTION 683
PROCESSING OF THE GnRH PRECURSOR 684
GnRH RECEPTORS AND SIGNALLING CASCADES 684
PHYSICAL STRUCTURE OF GnRH 688
BIOLOGICAL ACTIONS 688
PATHOPHYSIOLOGY 689
References 690
91: Brain Somatostatin-Related Peptides 691
ABSTRACT 691
DISCOVERY 691
STRUCTURE OF THE PRECURSOR mRNA/GENE 691
DISTRIBUTION OF THE mRNAs AND PEPTIDES 692
PROCESSING OF THE PRECURSORS AND DEGRADATION OF THE PEPTIDE 694
RECEPTORS AND SIGNALING CASCADES 694
INFORMATION ON ACTIVE AND/OR SOLUTION CONFORMATION 696
BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY 697
PATHOPHYSIOLOGICAL IMPLICATIONS 697
References 699
92: Corticotrophin-Releasing Hormone (CRH) Peptide Family 701
ABSTRACT 701
DISCOVERY 701
STRUCTURE OF THE PRECURSOR mRNA/GENE 702
DISTRIBUTION AND EXPRESSION OF mRNA 704
PROCESSING OF PREPROHORMONE 704
RECEPTORS AND BINDING PROTEINS 706
BIOLOGICAL ACTIONS IN THE CENTRAL NERVOUS SYSTEM 706
PATHOPHYSIOLOGICAL IMPLICATIONS 707
References 707
93: Growth Hormone-Releasing Hormone 709
ABSTRACT 709
DISCOVERY OF GHRH 709
STRUCTURE OF THE PRECURSOR mRNA/GENE 709
EXPRESSION OF GHRH IN THE BRAIN 710
PROCESSING OF GHRH PRECURSOR 711
GHRH RECEPTOR 711
GHRH SIGNALING 713
CONFORMATION OF GHRH AND SYNTHESIS OF ANALOGS 714
BIOLOGICAL ACTIVITY OF GHRH 714
PATHOPHYSIOLOGICAL IMPLICATIONS 715
References 715
94: PACAP/VIP 719
ABSTRACT 719
DISCOVERY 719
STRUCTURE OF THE PRECURSOR mRNA/GENE 719
DISTRIBUTION OF THE mRNA 720
PROCESSING OF THE PRECURSOR 720
RECEPTORS AND SIGNALING CASCADES 722
SOLUTION STRUCTURE COMPARISON 723
BIOLOGICAL ACTIONS IN THE BRAIN AND THE PITUITARY 723
PATHOPHYSIOLOGY OF PACAP/VIP 725
References 726
95: Neuropeptide Y 729
ABSTRACT 729
DISCOVERY OF NPY AND HOMOLOGS 729
STRUCTURE OF THE PRECURSOR mRNA/GENE 729
PROCESSING OF THE NPY PRECURSOR 731
DISTRIBUTION OF NPY mRNA AND PROTEIN 731
STRUCTURE OF NPY-LIKE PEPTIDES 732
RECEPTORS AND SIGNALING CASCADES 732
BIOLOGICAL ACTIONS 732
PATHOPHYSIOLOGICAL IMPLICATIONS 733
Acknowledgment 733
References 733
96: Melanocortins 735
ABSTRACT 735
DISCOVERY 735
STRUCTURE OF THE PROOPIOMELANOCORTIN mRNA/GENE 735
DISTRIBUTION OF POMC mRNA AND MELANOCORTINS IN THE BRAIN 736
PROCESSING OF PROOPIOMELANOCORTIN 737
CONTROL OF BIOSYNTHESIS AND RELEASE OF BRAIN MELANOCORTINS 738
MELANOCORTIN RECEPTOR FAMILY 738
STRUCTURE–ACTIVITY RELATIONSHIPS FOR MELANOCORTINS 738
BIOLOGICAL ACTIONS WITHIN THE BRAIN 739
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 741
References 741
97: Cocaine- and Amphetamine-Regulated Transcript (CART) 743
ABSTRACT 743
DISCOVERY 743
STRUCTURE OF THE PRECURSOR mRNA/GENE 743
PROCESSING OF CART PEPTIDES 743
DISTRIBUTION OF CART mRNA AND PEPTIDES 744
RECEPTORS AND SIGNALING CASCADES 745
BIOLOGICAL ACTIONS OF CART PEPTIDES WITHIN THE BRAIN AND PITUITARY 745
PHYSIOPATHOLOGICAL IMPLICATIONS 747
References 747
98: The Melanin-Concentrating Hormone 751
ABSTRACT 751
DISCOVERY 751
STRUCTURE OF THE PRECURSOR mRNA/GENE 752
DISTRIBUTION OF THE mRNA/PEPTIDES 754
PROCESSING OF THE MCH PRECURSOR 755
RECEPTORS AND SIGNALING CASCADES 755
ACTIVE STRUCTURE OF THE MCH PEPTIDE AND RECEPTOR CONFORMATION 757
BIOLOGICAL ACTIONS OF PRO-MCH-DERIVED PEPTIDES 757
PATHOPHYSIOLOGICAL IMPLICATIONS 758
References 759
99: CCK/Gastrin 761
ABSTRACT 761
DISCOVERY 761
STRUCTURE OF THE PRECURSOR mRNA/GENE 761
DISTRIBUTION OF CCK 761
PROCESSING OF THE PRECURSOR 762
RECEPTORS AND SIGNALING CASCADES 763
ACTIVE AND/OR SOLUTION CONFORMATION 764
BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY 764
PATHOPHYSIOLOGICAL IMPLICATIONS 765
References 765
100: The Hypocretins (Orexins) 767
ABSTRACT 767
DISCOVERY 767
STRUCTURE OF THE PRECURSOR mRNA/GENE 767
DISTRIBUTION OF THE mRNA 768
PROCESSING OF THE PRECURSOR 769
RECEPTORS AND SIGNALING CASCADES 769
INFORMATION ON ACTIVE AND/OR SOLUTION CONFORMATION 770
BIOLOGICAL ACTIONS WITHIN THE BRAIN 770
PATHOPHYSIOLOGICAL IMPLICATIONS 772
References 773
101: Ghrelin 777
ABSTRACT 777
DISCOVERY 777
STRUCURE OF THE PRECURSOR AND mRNA/GENE 777
DISTRIBUTION OF GHRELIN mRNA 778
PROCESSING OF THE GHRELIN PRECURSOR 778
RECEPTOR 780
BIOLOGICAL ACTIONS WITHIN THE BRAIN 780
PATHOPHYSIOLOGICAL IMPLICATIONS 780
References 781
102: Neurotensin 783
ABSTRACT 783
DISCOVERY OF NEUROTENSIN 783
STRUCTURE OF THE PRECURSOR mRNA/GENE 783
NT/N mRNA EXPRESSION IN BRAIN 784
PROCESSING OF THE PRECURSOR 784
RECEPTORS AND SIGNALING CASCADES 785
INFORMATION ON ACTIVE OR SOLUTION CONFORMATION 785
BRAIN FUNCTIONS 785
PATHOPHYSIOLOGICAL IMPLICATIONS 787
References 787
103: Neuromedin U (NMU): Brain Peptide 791
ABSTRACT 791
NMU DISCOVERY 791
STRUCTURE OF THE PRECURSOR mRNA/GENE 791
NMU DISTRIBUTION AND PROCESSING 791
NMU RECEPTORS 792
NMU1R 793
NMU2R 793
BIOLOGICAL ACTIONS OF NMU IN THE BRAIN 794
PATHOPHYSIOLOGICAL IMPLICATIONS 796
References 796
104: Galanin and GALP Systems in Brain—Molecular Pharmacology, Anatomy, and Putative Roles in Physiology and Pathology 799
ABSTRACT 799
DISCOVERY OF GALANIN AND GALANINLIKE PEPTIDE (GALP) 799
STRUCTURE AND REGULATION OF THE GALANIN AND GALP GENES 799
DISTRIBUTION OF GALANIN AND GALP mRNA AND PEPTIDE-IMMUNOREACTIVITY 800
NATURE AND PROCESSING OF GALANIN AND GALP PRECURSORS 800
GALANIN FAMILY RECEPTORS 801
CENTRAL ACTIONS OF GALANIN AND GALP IN NORMAL AND PATHOPHYSIOLOGY 802
References 806
105: Brain Tachykinins 809
ABSTRACT 809
DISCOVERY 809
STRUCTURE OF THE PRECURSOR mRNA/GENE 809
DISTRIBUTION OF THE mRNA 810
PROCESSING OF THE PRECURSOR 812
RECEPTORS AND SIGNALING CASCADES 813
ACTIVE AND SOLUTION CONFORMATION 813
BIOLOGICAL ACTIONS WITHIN THE BRAIN 814
PATHOPHYSIOLOGICAL IMPLICATIONS 815
References 815
106: CGRP and Adrenomedullin in the Brain 817
ABSTRACT 817
DISCOVERY 817
STRUCTURE OF THE PRECURSOR mRNA/GENE 817
DISTRIBUTION OF THE mRNA/PEPTIDE 819
CGRP 819
PROCESSING OF THE PRECURSOR 820
RECEPTORS AND SIGNALING CASCADES 821
PEPTIDE CONFORMATION 822
BIOLOGICAL ACTIONS WITHIN THE BRAIN 822
CGRP 822
PATHOLOGICAL IMPLICATIONS 823
Acknowledgments 823
References 823
107: The RFamide-Related Peptides 825
ABSTRACT 825
DISCOVERY OF THE MAMMALIAN RFAMIDERELATED PEPTIDES 825
STRUCTURE OF THE RFAMIDE-RELATED PEPTIDE PRECURSORS 825
PROCESSING OF THE RFAMIDE-RELATED PEPTIDE PRECURSORS 827
DISTRIBUTION OF RFAMIDE-RELATED PEPTIDES IN THE BRAIN 827
RFAMIDE-RELATED PEPTIDE RECEPTORS 829
INFORMATION ON SOLUTION CONFORMATION OF RFAMIDERELATED PEPTIDES 829
BIOLOGICAL ACTIONS OF RFAMIDERELATED PEPTIDES WITHIN THE BRAIN AND PITUITARY 829
References 830
108: Apelin: Discovery, Distribution, and Physiological Role 833
ABSTRACT 833
DISCOVERY 833
STRUCTURE OF THE PRECURSOR mRNA/GENE AND PROCESSING OF THE PRECURSOR 834
RECEPTORS AND SIGNALING CASCADES 834
DISTRIBUTION OF APELIN AND ITS RECEPTOR IN THE RAT BRAIN 835
BIOLOGICAL ACTIONS WITHIN THE BRAIN AND PITUITARY GLAND 835
PERIPHERAL CARDIOVASCULAR ACTIONS 838
CONCLUSION 838
Acknowledgments 838
References 838
109: Urotensin II and Urotensin II–Related Peptide 841
ABSTRACT 841
DISCOVERY 841
STRUCTURE 841
LOCALIZATION 842
RECEPTORS AND SIGNALING CASCADES 845
BIOLOGICAL ACTIONS WITHIN THE BRAIN 845
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL SIGNIFICANCE 846
References 846
110: Brain/B-Type Natriuretic Peptide (BNP) and C-Type Natriuretic Peptide (CNP) 851
ABSTRACT 851
DISCOVERY 851
STRUCTURE OF THE PRECURSOR mRNA AND GENE 853
DISTRIBUTION OF mRNA 853
PROCESSING OF PRECURSOR 855
RECEPTORS AND SIGNALING CASCADE 855
BIOLOGICAL ACTIONS IN THE BRAIN 856
PATHOPHYSIOLOGICAL IMPLICATIONS 856
References 857
111: Endozepines 859
ABSTRACT 859
DISCOVERY 859
STRUCTURE OF THE PRECURSOR mRNA/GENE 859
DISTRIBUTION OF DBI mRNA AND ENDOZEPINE IMMUNOREACTIVITY 859
PROCESSING OF DBI 861
RECEPTORS AND SIGNALING CASCADES 861
CONTROL OF BIOSYNTHESIS AND RELEASE OF ENDOZEPINES 862
INFORMATION ON SOLUTION CONFORMATION OF ENDOZEPINES 862
BIOLOGICAL ACTIONS OF ENDOZEPINES WITHIN THE BRAIN 863
PATHOPHYSIOLOGICAL IMPLICATIONS 863
References 864
112: KiSS-1/Metastin 867
ABSTRACT 867
DISCOVERY OF KiSS-1 SYSTEM 867
STRUCTURE OF THE KiSS-1 GENE 868
PROCESSING OF KiSS-1 PRECURSOR: THE KISSPEPTINS 868
DISTRIBUTION OF KiSS-1 mRNA/PROTEIN WITHIN THE BRAIN 868
GPR54 AS RECEPTOR FOR KISSPEPTINS: STRUCTURE AND SIGNALING CASCADES 870
BIOLOGICAL ACTIONS OF KiSSPEPTINS: BRAIN AND PITUITARY EFFECTS 870
PATHOPHYSIOLOGICAL IMPLICATIONS 872
Acknowledgments 873
References 873
XI: Endocrine Peptides Section 875
113: Role of Opioid Peptides in the Local Regulation of Endocrine Glands 875
ABSTRACT 875
INTRODUCTION 875
PITUITARY GLAND 875
PANCREATIC ISLETS 876
ADRENAL GLAND 876
CONCLUSION 877
References 877
114: Role of Tachykinin-Gene-Related Peptides in the Local Regulation of Endocrine Glands 879
ABSTRACT 879
INTRODUCTION 879
PITUITARY GLAND 879
THYROID GLAND 880
PARATHYROID GLAND 880
PANCREATIC ISLETS 880
ADRENAL GLAND 881
LEYDIG CELLS 881
OVARY 882
CONCLUSION 882
References 882
115: Neuropeptide Y and the Regulation of Endocrine Function 885
ABSTRACT 885
INTRODUCTION 885
NPY AND ADRENAL FUNCTION 885
NPY IN THE PANCREAS 886
NPY AND GONADAL FUNCTION 887
NPY AND THYROID FUNCTION 888
CONCLUSION 889
References 889
116: Effects of PACAP in the Local Regulation of Endocrine Glands 893
ABSTRACT 893
INTRODUCTION 893
EFFECTS ON THE PITUITARY GLAND 893
EFFECTS ON THE THYROID GLAND 895
EFFECTS OF PACAP ON THE ENDOCRINE TESTIS AND OVARY 895
EFFECTS OF PACAP ON THE ADRENAL 895
EFFECTS OF PACAP ON PANCREATIC ISLETS 896
References 897
117: Endothelins in the Local Regulation of Endocrine Glands 901
ABSTRACT 901
INTRODUCTION 901
PITUITARY GLAND 901
THYROID GLAND 902
PARATHYROID GLAND 902
PANCREATIC ISLETS 903
ADRENAL GLAND 903
LEYDIG CELLS 904
OVARY 904
CONCLUSION 905
References 905
118: Adrenomedullin and Related Peptides in the Local Regulation of Endocrine Glands 907
ABSTRACT 907
INTRODUCTION 907
PITUITARY 907
ADRENALS 908
ENDOCRINE PANCREAS 909
DIFFUSE ENDOCRINE SYSTEM OF THE GUT 910
OTHER ENDOCRINE ORGANS 910
CONCLUSION 911
Acknowledgments 911
References 911
119: Ghrelin in the Local Regulation of Endocrine Glands 915
ABSTRACT 915
INTRODUCTION 915
GHRELIN AND THE PITUITARY 915
GHRELIN AND THE THYROID 916
GHRELIN AND THE HEART AND CARDIOMYOCYTES 916
GHRELIN—A NOVEL PEPTIDE FOR CARTILAGE AND BONE HOMEOSTASIS 917
GHRELIN AND THE PANCREAS 917
GHRELIN AND THE ADRENAL CORTEX 918
GHRELIN AND THE REPRODUCTIVE SYSTEM 918
CONCLUSION 919
Acknowledgments 919
References 919
120: Atrial Natriuretic Peptide in Local Regulation of Endocrine Glands 923
ABSTRACT 923
DISCOVERY 923
STRUCTURE OF THE PRECURSOR mRNA GENE 923
DISTRIBUTION OF ANP mRNA 924
PROCESSING 924
RELEASE OF NPs 925
RECEPTORS AND SIGNALING CASCADE 925
BIOLOGICAL ACTIVITIES OF NPs 925
PATHOPHYSIOLOGICAL IMPLICATIONS 927
References 927
121: Galanin, Neurotensin, and Neuromedins in the Local Regulation of Endocrine Glands 929
ABSTRACT 929
INTRODUCTION 929
GALANIN 929
NEUROTENSIN 931
NEUROMEDINS 932
CONCLUSION 932
References 933
XII: Ingestive Peptides Section 935
122: Neuropeptide Y: A Conductor of the Appetite-Regulating Orchestra in the Hypothalamus 935
ABSTRACT 935
INTRODUCTION 935
NPY AND APPETITE 935
MECHANISM OF ACTION 936
REGULATION OF NPY SIGNALING AND APPETITE 937
PATHOPHYSIOLOGY 938
Acknowledgment 939
References 939
123: Hypothalamic Galanin and Ingestive Behavior: Relation to Dietary Fat, Alcohol, and Circulating Lipids 941
ABSTRACT 941
STIMULATORY EFFECTS OF GAL INJECTION ON INGESTIVE BEHAVIOR 941
EFFECTS PRODUCED BY MUTATIONS OF THE GAL GENE OR GAL RECEPTOR GENES 942
EFFECTS OF CIRCULATING HORMONES AND DIETARY CONDITIONS ON ENDOGENOUS GAL 942
SITES OF ACTION AND NEURAL NETWORKS AFFECTED 943
RECEPTORS AND SIGNALING PATHWAYS MEDIATING GAL EFFECTS ON INGESTIVE BEHAVIOR 944
GAL IN RELATION TO OTHER PEPTIDERGIC AND AMINERGIC SYSTEMS CONTROLLING INGESTIVE BEHAVIOR 944
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONSEQUENCES OF GAL’S ACTIONS 944
Acknowledgments 945
References 945
124: Effects of Melanocortins on Ingestive Behavior 949
ABSTRACT 949
EFFECTS OF THE MELANOCORTINS ON FEEDING BEHAVIOR 949
GENETIC STUDIES ON MELANOCORTIN ACTION 950
FUNCTIONAL RESPONSE OF THE MELANOCORTINS TO DIFFERING METABOLIC AND FEEDING STATES 951
NEUROANATOMY OF THE CENTRAL MELANOCORTIN SYSTEM 953
RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR MELANOCORTIN ACTIONS ON INGESTIVE BEHAVIOR 954
INTERACTIONS OF THE MELANOCORTINS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS 955
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 955
References 956
125: CART Peptide and Ingestive Behavior 959
ABSTRACT 959
DESCRIPTION OF CART PEPTIDE EFFECTS ON FEEDING BEHAVIOR 959
STUDIES FROM GENETIC MANIPULATIONS OR MUTATIONS 959
FUNCTIONAL RESPONSE OF CART TO DIFFERING METABOLIC AND FEEDING STATES 960
SITES OF ACTION AND NEURAL NETWORKS AFFECTED 960
RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR INGESTIVE BEHAVIORS 961
INTERACTIONS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS 961
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 962
References 962
126: Orexins and Opioids in Feeding Behavior 965
ABSTRACT 965
EFFECT OF OREXINS AND OPIOIDS ON FEEDING BEHAVIOR 965
STUDIES FROM GENETIC MANIPULATIONS OR MUTATIONS 967
FUNCTIONAL RESPONSE OF OREXINS AND OPIOIDS TO METABOLIC AND FEEDING STATES 967
OxA AND OPIOID LIGANDS AND RECEPTORS: SITES OF ACTION AND NEURAL NETWORKS AFFECTED 968
INTERACTIONS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS 969
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 969
INTERACTION BETWEEN OxA AND OPIOIDS 970
CONCLUSION 970
References 970
127: Melanin-Concentrating Hormone 975
ABSTRACT 975
INTRODUCTION 975
EFFECTS OF MCH ON FEEDING BEHAVIOR 975
STUDIES FROM GENETIC MANIPULATIONS OR MUTATIONS 976
FUNCTIONAL RESPONSE OF THE PEPTIDE/GENE TO DIFFERING METABOLIC AND FEEDING STATES 976
SITES OF ACTION AND NEURAL NETWORKS AFFECTED 977
RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR THE INGESTIVE EFFECTS 978
INTERACTIONS WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS 978
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 978
References 979
128: Corticotrophin-Releasing Hormone (CRH) and Ingestive Behavior 983
ABSTRACT 983
EFFECTS OF CRH AND UROCORTINS ON FEEDING BEHAVIOR 983
STUDIES FROM GENETIC MANIPULATIONS 984
METABOLIC REGULATION OF CRH AND CRH RECEPTORS 984
SITES OF ACTION AND NETWORKS MEDIATING CRH EFFECTS 984
RECEPTORS AND PATHWAYS MEDIATING THE EFFECTS OF CRH AND THE UROCORTINS ON FOOD INTAKE 985
INTERACTIONS WITH NEUROPEPTIDE SYSTEMS 985
PHYSIOLOGY AND PATHOPHYSIOLOGICAL IMPLICATIONS 986
References 986
129: Peptide YY (PYY) and Neuromedin U (NMU): Effects on Ingestive Behavior 991
ABSTRACT 991
INTRODUCTION 991
DISCOVERY 992
DISTRIBUTION AND RELEASE 992
RECEPTORS 992
THE ROLE OF NMU IN THE REGULATION OF ENERGY BALANCE 993
PYY 994
CONCLUSION 995
References 995
130: Ghrelin and Ingestive Behavior 999
ABSTRACT 999
GHRELIN ADMINISTRATION INDUCES FOOD INTAKE ACROSS SPECIES 999
THE GROWTH HORMONE SECRETAGOGUE RECEPTOR GHSR-1a MEDIATES GHRELIN-INDUCED FOOD INTAKE 1000
GHRELIN TARGETS THE HYPOTHALAMUS TO INCREASE FOOD INTAKE AND BODY WEIGHT 1000
OTHER HYPOTHALAMIC PATHWAYS INVOLVED IN GHRELIN-INDUCED HYPERPHAGIA 1001
EXTRA-HYPOTHALAMIC EFFECTS OF GHRELIN ON FOOD INTAKE 1002
PERIPHERAL GHRELIN LEVELS ARE REGULATED BY FOOD INTAKE 1002
References 1004
131: Cholecystokinin and Satiety 1007
ABSTRACT 1007
INTRODUCTION 1007
FEEDING ACTIONS OF PERIPHERAL CCK 1007
FEEDING ACTIONS OF CENTRAL CCK 1009
STUDIES WITH OLETF RATS AND CCK-A RECEPTOR KNOCKOUT MICE 1009
FUNCTIONAL RESPONSES TO PERIPHERAL CCK IN DIFFERING METABOLIC STATES 1010
SITES OF ACTION FOR PERIPHERAL CCK IN SATIETY 1011
RECEPTORS AND SIGNALING PATHWAYS MEDIATING CCK SATIETY 1011
INTERACTIONS WITH OTHER SIGNALING SYSTEMS 1012
PATHOPHYSIOLOGIAL IMPLICATIONS 1012
References 1012
132: Enterostatin, a Peptide Regulator of Dietary Fat Ingestion 1015
ABSTRACT 1015
INTRODUCTION 1015
ENTEROSTATIN EFFECTS ON FEEDING BEHAVIOR 1015
GENOMIC STUDIES 1016
FUNCTIONAL RESPONSES TO DIFFERING FEEDING AND METABOLIC CONDITIONS 1016
SITES OF ACTION AND NEURAL NETWORKS AFFECTED 1017
RECEPTORS AND SIGNALING PATHWAYS 1018
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 1019
References 1019
133: Regulation of Feeding Behavior by Glucagonlike Peptide 1 (GLP-1) 1021
ABSTRACT 1021
EFFECTS OF GLP-1 ON FEEDING BEHAVIOR 1021
STUDIES FROM GENETIC MANIPULATIONS (KNOCKOUTS, TRANSGENICS) AND SYNTHETIC ANALOGS 1021
FUNCTIONAL RESPONSE OF THE GLP-1 PEPTIDE/GENE TO DIFFERING METABOLIC AND FEEDING STATES 1022
SITES OF ACTION AND NEURAL NETWORKS AFFECTED BY GLP-1 1022
GLP-1 RECEPTORS AND SIGNALING PATHWAYS RESPONSIBLE FOR THE INGESTIVE EFFECTS 1022
INTERACTIONS OF GLP-1 WITH OTHER PEPTIDERGIC/AMINERGIC SYSTEMS 1023
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 1023
References 1024
134: Role of Amylin and Calcitonin-Gene-Related Peptide (CGRP) in the Control of Food Intake 1027
ABSTRACT 1027
INTRODUCTION 1027
CHARACTERIZATION OF THE EFFECTS OF AMYLIN AND CGRP ON FOOD INTAKE 1027
FOOD INTAKE IN KNOCKOUT ANIMALS 1028
FOOD INTAKE IN ANIMALS OVEREXPRESSING AMYLIN 1029
FOOD INTAKE IN ANIMALS DEFICIENT OF CGRP OR OVEREXPRESSING CGRP 1029
REGULATION OF AMYLIN AND CGRP SYNTHESIS AND SECRETION 1029
CENTRAL PATHWAYS MEDIATING THE ANORECTIC EFFECTS OF AMYLIN AND CGRP 1029
HYPOTHALAMIC INVOLVEMENT IN THE ANORECTIC ACTION OF PERIPHERAL AMYLIN 1030
RECEPTORS AND SIGNALING PATHWAYS 1030
INTERACTION WITH OTHER PEPTIDES REGULATING INGESTIVE BEHAVIOR 1031
INTERACTION BETWEEN AMYLIN AND METABOLITES 1031
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 1031
CONCLUSION 1031
References 1031
135: Leptin and the Regulation of Feeding 1033
ABSTRACT 1033
LEPTIN AND FEEDING BEHAVIOR 1033
THE ABSENCE OF LEPTIN ACTION 1033
FUNCTIONAL RESPONSES TO LEPTIN DURING ALTERED METABOLIC STATES 1034
SITES OF LEPTIN ACTION 1034
LEPTIN RECEPTORS AND INTRACELLULAR SIGNALING PATHWAYS 1034
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 1036
References 1037
136: Ingestive Peptides: Insulin 1039
ABSTRACT 1039
INTRODUCTION 1039
EFFECTS OF INSULIN ON FEEDING BEHAVIOR 1039
GENETIC AND MOLECULAR BIOLOGICAL MANIPULATIONS 1041
METABOLIC STATES 1041
SITE OF ACTION AND NEURAL NETWORKS AFFECTED 1042
RECEPTORS AND SIGNALING PATHWAYS 1042
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS 1042
CONCLUSION 1043
References 1043
XIII: Gastrointestinal Peptides Section 1045
137: Adrenomedullin in Gastrointestinal Function 1045
ABSTRACT 1045
INTRODUCTION 1045
STRUCTURE 1045
EXPRESSION AND DISTRIBUTION 1046
RELEASE 1046
RECEPTORS AND SIGNAL TRANSDUCTION PATHWAYS 1046
BIOLOGICAL ACTIONS 1047
CONCLUSION 1048
Acknowledgment 1048
References 1048
138: Calcitonin Gene-Related Peptide and Gastrointestinal Function 1051
ABSTRACT 1051
INTRODUCTION 1051
DISTRIBUTION OF CGRP IN THE GI TRACT 1051
CGRP RECEPTORS IN THE GI TRACT 1052
RELEASE OF CGRP IN THE GI TRACT 1053
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS OF CGRP IN THE GI TRACT 1053
References 1056
139: Peripheral Cholecystokinin 1059
ABSTRACT 1059
DISCOVERY 1059
STRUCTURE OF THE PRECURSOR mRNA/GENE 1060
CHOLECYSTOKININ PEPTIDE DISTRIBUTION 1060
PROCESSING OF PREPROCHOLECYSTOKININ 1060
MOLECULAR FORMS OF CHOLECYSTOKININ 1062
CHOLECYSTOKININ RECEPTORS 1062
SOLUTION CONFORMATION 1063
PERIPHERAL BIOLOGICAL ACTIONS OF CHOLECYSTOKININ 1064
CONCLUSION 1066
References 1066
140: Corticotrophin-Releasing Hormone (CRH) Family in the Gastrointestinal System 1069
ABSTRACT 1069
INTRODUCTION 1069
EXPRESSION AND LOCATION OF CRH PEPTIDES AND RECEPTORS IN THE GI SYSTEM 1069
ACTIONS OF CRH AND RELATED PEPTIDES IN GI FUNCTIONS 1070
NEURONAL PATHWAYS INVOLVED IN CRH ACTIONS IN GI FUNCTIONS 1072
PATHOPHYSIOLOGICAL IMPLICATIONS 1072
Acknowledgment 1073
References 1073
141: Paneth Cell a-Defensins 1075
ABSTRACT 1075
DISCOVERY OF ENTERIC PANETH CELL a-DEFENSINS 1075
a-DEFENSIN GENE AND PRECURSOR STRUCTURES 1076
DISTRIBUTION OF a-DEFENSINS IN THE GASTROINTESTINAL TRACT 1078
STRUCTURES OF PANETH CELL a-DEFENSINS 1078
MECHANISMS OF ACTION 1078
PATHOPHYSIOLOGICAL IMPLICATIONS 1080
Acknowledgments 1080
References 1080
142: Galanin in the Gastrointestinal Tract: Distribution and Function 1083
ABSTRACT 1083
INTRODUCTION 1083
GALANIN DISTRIBUTION 1083
BIOLOGICAL EFFECTS OF GALANIN IN THE GASTROINTESTINAL TRACT 1084
GALANIN RECEPTORS 1084
INFLAMMATION AND INJURY 1087
Acknowledgment 1087
References 1087
143: Gastrin 1089
ABSTRACT 1089
DISCOVERY 1089
STRUCTURE OF THE GENE AND PRECURSOR 1089
DISTRIBUTION OF MRNA IN GUT 1090
RECEPTOR EXPRESSION AND REGULATION 1090
BIOLOGICAL ACTIONS ON GI TRACT 1090
PATHOPHYSIOLOGICAL IMPLICATIONS 1091
References 1091
144: Gastrin-Releasing Peptide 1093
ABSTRACT 1093
INTRODUCTION 1093
STRUCTURE OF THE PRECURSOR mRNA/GENE AND PEPTIDE VARIANTS 1093
DISTRIBUTION OF GRP-LIKE IMMUNOREACTIVITY, GRP mRNA, AND GRP RECEPTOR 1094
RECEPTOR SUBTYPES AND SIGNALING 1095
BIOLOGICAL ACTIONS WITHIN THE GI TRACT 1095
PATHOPHYSIOLOGICAL IMPLICATIONS 1099
References 1100
145: Glucagonlike Peptides 1 and 2, Enteroglucagon, Glicentin, and Oxyntomodulin 1103
ABSTRACT 1103
DISCOVERY AND STRUCTURE OF THE GENE 1103
EXPRESSION OF THE GENE 1104
ACTIVE CONFORMATION AND METABOLISM 1105
RECEPTOR EXPRESSION 1105
BIOLOGICAL ACTIONS 1106
ACTIONS OF GLP-1 1106
PATHOPHYSIOLOGICAL IMPLICATIONS 1109
References 1110
146: Ghrelin 1111
ABSTRACT 1111
ALTERNATIVE DISCOVERIES OF GHRELIN 1111
STRUCTURE OF THE PRECURSOR mRNA/GENE 1111
DISTRIBUTION IN THE GASTROINTESTINAL TRACT 1112
STRUCTURE–ACTIVITY RELATIONS OF GHRELIN AND OF THE GHRELIN RECEPTOR 1112
BIOLOGICAL ACTION ON THE GASTROINTESTINAL TRACT 1113
PATHOPHYSIOLOGICAL IMPLICATIONS AND THERAPEUTIC POTENTIAL 1114
Acknowledgments 1115
References 1115
147: Leptin and the Gastrointestinal Tract 1117
ABSTRACT 1117
INTRODUCTION 1117
THE STOMACH PRODUCES LEPTIN 1117
GASTRIC LEPTIN IS A NEUROENDOCRINE MOLECULE FOR SATIETY 1118
GASTRIC LEPTIN ENTERS THE INTESTINE 1118
LEPTIN REGULATES INTESTINAL ENDOCRINE SECRETIONS 1118
GUT LEPTIN AND INTESTINAL ABSORPTION OF NUTRIENTS 1119
LEPTIN AND GUT PATHOLOGIES 1120
CONCLUSION 1120
Acknowledgments 1121
References 1121
148: Motilin 1123
ABSTRACT 1123
DISCOVERY OF MOTILIN 1123
STRUCTURE OF MOTILIN AND RELATED PEPTIDES 1123
DISTRIBUTION IN THE GI TRACT 1125
STRUCTURE–ACTIVITY 1126
RECEPTOR 1126
BIOLOGICAL ACTIONS 1127
PATHOPHYSIOLOGICAL IMPLICATION 1129
Acknowledgments 1129
References 1130
149: Neurotensin in Regulation of Gastrointestinal Functions 1131
ABSTRACT 1131
INTRODUCTION 1131
NT INHIBITS MOTILITY AND SECRETION IN THE STOMACH AND SMALL INTESTINE 1132
NT ENHANCES COLONIC MOTILITY AND STIMULATES SECRETION 1132
ROLE OF NT AND NTR1 IN INTESTINAL INFLAMMATION 1133
NT PROMOTES CELL GROWTH, REGENERATION, AND HEALING OF THE GI MUCOSA 1133
NT AND COLONIC STRESS RESPONSES 1133
CONCLUSION 1134
References 1134
150: Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) 1137
ABSTRACT 1137
PACAP IS A NEWLY DISCOVERED NEUROENTERIC PEPTIDE 1137
CLONING AND CHARACTERIZATION OF PAC1 1137
SIGNAL TRANSDUCTION OF PAC1 1138
LOCALIZATION OF PAC1 1138
PHYSIOLOGY OF PAC1 IN THE GASTROINTESTINAL TRACT 1139
CONCLUSION 1140
Acknowledgments 1140
References 1140
151: Pancreatic Polypeptide 1143
ABSTRACT 1143
DISCOVERY OF PANCREATIC POLYPEPTIDE AS IT RELATES TO THE GASTROINTESTINAL TRACT 1143
STRUCTURE OF THE PRECURSOR mRNA/GENE AND PEPTIDE VARIANTS 1144
DISTRIBUTION OF THE mRNA AND PROTEIN 1144
RECEPTOR SUBTYPES, SIGNALING, AND DISTRIBUTION 1145
BIOLOGICAL ACTIONS 1147
PHYSIOPATHOLOGICAL IMPLICATIONS 1149
References 1150
152: Peptide YY 1155
ABSTRACT 1155
INTRODUCTION 1155
STRUCTURE OF THE PYY GENE AND PYY BIOSYNTHESIS 1155
GASTROINTESTINAL DISTRIBUTION AND ONTOGENY OF INTESTINAL PYY 1155
REGULATION OF PYY SECRETION 1156
PYY RECEPTORS 1157
BIOLOGICAL ACTIONS ON THE GASTROINTESTINAL TRACT 1158
GROWTH PROMOTING ACTIONS OF PYY ON THE GASTROINTESTINAL TRACT 1159
INHIBITORY ACTION OF PYY(3–36) ON APPETITE AND FOOD INTAKE 1159
PATHOPHYSIOLOGY OF PYY 1159
References 1159
153: Secretin 1161
ABSTRACT 1161
DISCOVERY OF SECRETIN 1161
STRUCTURE OF SECRETIN, ITS PRECURSOR TRANSCRIPT, AND GENE 1161
DISTRIBUTION OF SECRETIN AND ITS mRNA 1162
SECRETIN RECEPTOR SUBTYPES, DISTRIBUTION, AND SIGNALING 1164
BIOLOGICAL ACTIONS OF SECRETIN IN THE GASTROINTESTINAL TRACT 1164
PATHOPHYSIOLOGY AND CLINICAL APPLICATION OF SECRETIN 1167
References 1167
154: Somatostatin 1169
ABSTRACT 1169
INTRODUCTION 1169
SOMATOSTATIN-14, SOMATOSTATIN-28 AND CORTISTATIN IN THE GASTROINTESTINAL TRACT 1169
SOMATOSTATIN RECEPTORS IN THE GASTROINTESTINAL TRACT 1170
BIOLOGICAL ACTION OF SOMATOSTATIN IN THE GASTROINTESTINAL TRACT 1170
SOMATOSTATIN AND SOMATOSTATIN RECEPTORS IN THE DISEASED GASTROINTESTINAL TRACT 1171
SOMATOSTATIN ANALOGS AND THEIR CLINICAL APPLICATIONS IN GASTROINTESTINAL DISEASE 1172
References 1173
155: Somatostatin Analogs in theGastrointestinal Tract 1177
ABSTRACT 1177
INTRODUCTION 1177
GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS 1177
SECRETORY DIARRHEAS 1179
ESOPHAGEAL VARICEAL HEMORRHAGE 1180
GI MOTILITY AND FUNCTIONAL GI DISORDERS 1180
POSTOPERATIVE COMPLICATIONS OF SURGERY 1181
BILIARY SYSTEM 1182
References 1182
156: Substance P and Related Tachykinins in the Gastrointestinal Tract 1185
ABSTRACT 1185
DISCOVERY OF TACHYKININS IN THE GUT 1185
DISTRIBUTION OF TACHYKININ mRNAS AND PEPTIDES IN THE GI TRACT 1185
TACHYKININ RECEPTOR SUBTYPES, SIGNALING, AND DISTRIBUTION IN THE GI TRACT 1186
BIOLOGICAL ACTIONS OF TACHYKININS IN THE GUT 1187
PATHOPHYSIOLOGICAL IMPLICATIONS OF TACHYKININS IN THE GI TRACT 1188
Acknowledgments 1190
References 1191
157: TFF (Trefoil Factor Family) Peptides 1193
ABSTRACT 1193
DISCOVERY 1193
STRUCTURE OF THE PRECURSOR mRNA/GENE 1193
EXPRESSION IN THE GI TRACT 1194
ACTIVE CONFORMATION, 3D STRUCTURE 1196
TFF RECEPTORS AND SIGNALING CASCADES 1196
BIOLOGICAL ACTIONS ON THE GI TRACT 1196
PATHOPHYSIOLOGICAL IMPLICATIONS 1198
Acknowledgments 1199
References 1199
158: Signaling by Vasoactive Intestinal Peptide in Gastrointestinal Smooth Muscle 1201
ABSTRACT 1201
INTRODUCTION 1201
INTERPLAY OF INHIBITORY NEUROTRANSMITTERS 1202
VIP RECEPTORS AND THEIR SIGNALING IN SMOOTH MUSCLE 1202
Acknowledgments 1205
References 1205
XIV: Cardiovascular Peptides Section 1209
159: Adrenomedullin and Its Related Peptides 1209
ABSTRACT 1209
DISCOVERY AND STRUCTURE OF AM 1209
STRUCTURE OF THE PRECURSOR mRNA/GENE 1209
DISTRIBUTION OF THE mRNA AND PEPTIDE IN THE CARDIOVASCULAR SYSTEM 1210
RECEPTORS AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM 1211
BIOLOGICAL ACTIONS IN THE CARDIOVASCULAR SYSTEM 1211
PROADRENOMEDULLIN N-TERMINAL 20 PEPTIDE 1212
INFORMATION ON MOLECULAR FORM OF AM 1213
CLINICAL IMPLICATION OF AM IN CARDIOVASCULAR DISEASES 1213
CONCLUSION 1213
References 1214
160: Angiotensin II and Its Related Peptides 1215
ABSTRACT 1215
DISCOVERY 1215
STRUCTURE OF THE PEPTIDE AND COMPONENT OF RA SYSTEM 1215
DISTRIBUTION OF RA SYSTEM, PROCESSING, AND ENDOGENOUS FORM IN THE CARDIOVASCULAR SYSTEM 1216
RECEPTORS AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM 1216
BIOLOGICAL ACTIONS AND PATHOPHYSIOLOGICAL IMPLICATION IN THE CARDIOVASCULAR SYSTEM 1217
References 1219
161: Bradykinin and Its Related Peptides 1221
ABSTRACT 1221
DISCOVERY 1221
STRUCTURE OF KININOGEN mRNA AND GENE 1221
DISTRIBUTION OF KININOGEN AND KALLIKREIN mRNA AND KININ PEPTIDES 1222
FORMATION OF KININ PEPTIDES 1222
METABOLISM OF KININ PEPTIDES 1223
KININ RECEPTORS AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM 1224
ROLE OF KININ PEPTIDES IN HEALTH AND DISEASE STATES 1224
References 1224
162: Calcitonin Gene-Related Peptides 1227
ABSTRACT 1227
CALCITONIN GENE-RELATED PEPTIDE 1227
Acknowledgments 1230
References 1230
163: Endothelins 1233
ABSTRACT 1233
DISCOVERY 1233
STRUCTURE OF THE PRECURSOR mRNA/GENE AND PROCESSING 1233
PLASMA CONCENTRATION AND INACTIVATION OF ENDOTHELIN 1 1235
RECEPTORS AND THEIR DISTRIBUTION 1236
BIOLOGICAL ACTIONS IN THE CARDIOVASCULAR SYSTEM 1237
References 1238
164: Ghrelin: Its Therapeutic Potential in Heart Failure 1239
ABSTRACT 1239
INTRODUCTION 1239
DISCOVERY, STRUCTURE, AND SYNTHESIS 1240
RECEPTORS AND THEIR DISTRIBUTION 1240
BIOLOGICAL ACTINS 1240
CLINICAL APPLICATION OF GHRELIN 1241
CONCLUSION 1242
References 1242
165: Natriuretic Peptides in the Cardiovascular System 1245
ABSTRACT 1245
DISCOVERY OF NATRIURETIC PEPTIDES 1245
STRUCTURE OF THE PRECURSORS, mRNAs, AND GENES OF NPs 1246
DISTRIBUTION OF THE mRNA AND PEPTIDE IN THE CARDIOVASCULAR SYSTEM 1247
PROCESSING AND ENDOGENOUS FORMS OF NPs 1248
RECEPTORS OF NPs AND THEIR DISTRIBUTION IN THE CARDIOVASCULAR SYSTEM 1248
INFORMATION ON ACTIVE AND/OR SOLUTION CONFORMATION OF NPs 1249
BIOLOGICAL ACTIONS OF NPs IN THE CARDIOVASCULAR SYSTEM 1249
PATHOPHYSIOLOGICAL IMPLICATION OF NPs IN THE CARDIOVASCULAR SYSTEM 1250
References 1252
166: Urotensin and Its Related Peptides 1255
ABSTRACT 1255
INTRODUCTION 1255
UROCORTIN (UROTENSIN I) 1255
UROTENSIN II 1257
CONCLUSION 1258
References 1258
167: Vasoactive Intestinal Peptide 1261
ABSTRACT 1261
INTRODUCTION 1261
DISCOVERY 1262
DISTRIBUTION 1262
PROCESSING 1262
RECEPTORS 1263
BIOLOGICAL ACTIONS 1264
PATHOPHYSIOLOGY 1266
Acknowledgments 1267
References 1267
168: Cardiovascular Peptides: Vasopressin 1269
ABSTRACT 1269
DISCOVERY 1269
STRUCTURE OF THE PRECURSOR mRNA/GENE 1269
DISTRIBUTION OF THE mRNA 1269
PROCESSING 1269
RECEPTORS 1270
ACTIVE OR SOLUTION CONFORMATION 1270
BIOLOGICAL ACTIVITY 1270
PATHOPHYSIOLOGICAL IMPLICATIONS 1271
References 1272
XV: Renal Peptides Section 1273
169: Renal Effects of Neurohypophyseal Peptides 1273
ABSTRACT 1273
BRIEF HISTORY AND OVERVIEW OF THE NEUROHYPOPHYSEAL PEPTIDES 1273
BODY FLUID HOMEOSTASIS 1274
VASOPRESSIN AND OXYTOCIN RECEPTORS 1274
LOCALIZATION OF VASOPRESSIN AND OXYTOCIN RECEPTORS IN THE KIDNEY 1275
RENAL EFFECTS OF VASOPRESSIN 1275
RENAL EFFECTS OF OXYTOCIN 1277
References 1277
170: Renal Renin-Angiotensin System 1281
ABSTRACT 1281
INTRODUCTION 1281
DISTRIBUTION OF RENIN, ANGIOTENSINCONVERTING ENZYME, AND ANGIOTENSINOGEN IN THE KIDNEY 1281
INTRARENAL LEVELS OF ANGIOTENSIN II 1284
BIOLOGICAL ACTIONS OF INTRARENAL ANG II 1285
CONCLUSION 1286
References 1286
171: Renal Natriuretic Peptide System and Actions of Urodilatin 1289
ABSTRACT 1289
DISCOVERY AND FIRST DESCRIPTIONS OF URODILATIN 1289
METABOLISM OF URODILATIN IN THE KIDNEY AND ITS PHYSIOLOGICAL AND PHARMACOLOGICAL SIGNIFICANCE 1292
URODILATIN—CLINICAL IMPLICATIONS 1293
References 1294
172: ANP and Its Role in the Regulation of Renal Tubular Transport Processes 1297
ABSTRACT 1297
DISCOVERY OF ATRIAL NATRIURETIC PEPTIDE ACTIONS IN THE KIDNEY 1297
EFFECTS OF ANP ON TUBULAR TRANSPORT SYSTEMS 1297
References 1301
173: Adrenomedullin as a Renal Peptide 1303
ABSTRACT 1303
ADRENOMEDULLIN PEPTIDE 1303
AM RECEPTOR 1303
RENAL BIOLOGICAL ACTIONS OF AM 1304
RENOPROTECTIVE ACTIONS OF AM 1304
CLINICAL IMPLICATIONS OF AM IN ASSOCIATION WITH THE KIDNEY 1304
References 1305
174: Adrenomedullin 2/Intermedin 1309
ABSTRACT 1309
DISCOVERY 1309
STRUCTURE OF THE PRECURSOR mRNA AND GENE 1310
DISTRIBUTION OF mRNA 1312
PROCESSING OF THE PRECURSOR 1312
RECEPTORS AND SIGNALING CASCADE 1312
PATHOPHYSIOLOGICAL IMPLICATIONS 1313
References 1314
175: Renal Endothelin 1315
ABSTRACT 1315
BRIEF HISTORY OF ENDOTHELIN 1315
LOCALIZATION OF THE ET-1 SYSTEM IN THE KIDNEY 1315
RENAL HEMODYNAMIC EFFECTS OF ET-1 1316
ET-1 EFFECTS ON EXCRETORY FUNCTION 1316
RENAL ET-1 IN BLOOD PRESSURE REGULATION 1318
CONCLUSION 1319
References 1319
176: Prolactin and Kidney Function 1323
ABSTRACT 1323
INTRODUCTION 1323
CLASSICAL PRODUCTION SITE AND ACTIONS OF PROLACTIN 1323
PROLACTIN RECEPTORS 1324
PROLACTIN AND OSMOREGULATION 1324
PROLACTIN RECEPTORS IN THE MAMMALIAN KIDNEY 1324
RENAL PRODUCTION OF PROLACTIN 1325
RENAL ACTIONS OF PROLACTIN 1325
PROLACTIN AND RENAL FUNCTION IN HUMANS 1326
THE JURY IS STILL OUT ON THE RENAL ACTIONS OF PROLACTIN 1326
HAVE TRANSGENE METHODS CLARIFIED THE ISSUE? 1327
References 1327
XVI: Respiratory Peptides Section 1329
177: Therapeutic Potential of Adrenomedullin for Pulmonary Hypertension 1329
ABSTRACT 1329
INTRODUCTION 1329
DISCOVERY, STRUCTURE, AND SYNTHESIS 1329
RECEPTORS AND THEIR DISTRIBUTION 1329
BIOLOGICAL ACTIONS 1330
CLINICAL APPLICATION OF AM FOR PULMONARY HYPERTENSION 1331
CONCLUSION 1333
References 1333
178: Endothelin in the Airways 1335
ABSTRACT 1335
INTRODUCTION 1335
SYNTHESIS AND ELIMINATION OF ET-1 1336
ENDOTHELIN RECEPTOR SUBTYPES AND LOCALIZATION 1336
PATHOPHYSIOLOGICAL ROLE 1336
References 1337
179: PACAP’s Role in Pulmonary Function 1339
ABSTRACT 1339
GENE STRUCTURE AND DISTRIBUTION OF THE PRECURSOR mRNA 1339
RECEPTORS 1339
BIOLOGICAL ACTIONS WITHIN THE LUNG 1340
PATHOPHYSIOLOGICAL IMPLICATIONS 1342
THERAPEUTIC POTENTIAL 1343
References 1344
180: Tachykinins and Their Receptors in the Lung 1347
ABSTRACT 1347
TACHYKININ RECEPTOR PHARMACOLOGY 1347
TACHYKININ LOCALIZATION IN THE LUNG 1348
TACHYKININ RECEPTOR DISTRIBUTION IN THE LUNG 1348
TACHYKININ-MEDIATED BIOLOGICAL EFFECTS IN THE LUNG 1348
THERAPEUTIC POTENTIAL OF TACHYKININ NK1 RECEPTOR BLOCKADE 1349
THERAPEUTIC POTENTIAL OF TACHYKININ NK2 RECEPTOR BLOCKADE 1349
THERAPEUTIC POTENTIAL OF DUAL TACHYKININ NK1-NK2 RECEPTOR BLOCKADE 1349
THERAPEUTIC POTENTIAL OF BLOCKADE OF THE TACHYKININ NK3 RECEPTOR 1350
CONCLUSION 1350
References 1350
181: Vasoactive Intestinal Peptide 1353
ABSTRACT 1353
INTRODUCTION: VIP IN THE LUNG 1353
VIP AND ITS FAMILY OF PEPTIDES 1353
DISTRIBUTION AND LOCALIZATION 1353
BIOLOGICAL ACTIONS PERTINENT TO THE LUNG 1354
RECEPTORS 1355
SIGNAL TRANSDUCTION PATHWAYS 1355
PHYSIOLOGICAL ROLES 1355
VIP IN PULMONARY DISEASE 1355
THERAPEUTIC POTENTIAL 1356
References 1357
XVII: Opioid Peptides Section 1359
182: Proenkephalin-Derived Opioid Peptides 1359
ABSTRACT 1359
DISCOVERY OF THE ENKEPHALINS 1359
STRUCTURE OF THE PRECURSOR GENE 1359
DISTRIBUTION OF ENKEPHALIN mRNA AND PEPTIDE 1359
PROCESSING 1360
RECEPTORS 1360
BIOLOGICAL ACTIVITY OF ENKEPHALINS 1361
PATHOPHYSIOLOGICAL IMPLICATIONS 1362
References 1363
183: Prodynorphin-Derived Opioid Peptides 1365
ABSTRACT 1365
DISCOVERY 1365
STRUCTURE OF THE PRECURSOR mRNA/GENE 1365
PROCESSING 1366
RECEPTORS 1367
CONFORMATIONAL ANALYSIS OF DYN A(1–17) 1367
DYNORPHIN EXPRESSION IN THE CENTRAL NERVOUS SYSTEM AND POSSIBLE BIOLOGICAL ACTIONS 1367
PATHOPHYSIOLOGICAL IMPLICATIONS 1368
DRUG ABUSE AND DYNORPHINS 1369
DYNORPHIN EXPRESSION IN PERIPHERAL TISSUES 1369
PERSPECTIVE 1370
References 1370
184: POMC Opioid Peptides 1371
ABSTRACT 1371
INTRODUCTION 1371
DISCOVERY 1371
DISTRIBUTION 1371
PROCESSING 1372
RECEPTORS 1373
BIOLOGICAL ACTIONS 1374
PATHOPHYSIOLOGICAL IMPLICATIONS 1376
References 1376
185: Endomorphins as Endogenous Peptides for u-Opioid Receptor: Their Differences in the Pharmacological and Physiological Characters 1379
ABSTRACT 1379
DISCOVERY OF ENDOMORPHINS 1379
DISTRIBUTION OF THE ENDOMORPHIN-2- LIKE IMMUNOREACTIVE NEURONS IN THE CENTRAL NERVOUS SYSTEM 1380
DISTRIBUTION OF THE EM-1-LI NEURONS IN THE CENTRAL NERVOUS SYSTEM 1380
RECEPTOR SELECTIVITY AND ITS MODULATION 1381
BIOLOGICAL ACTIONS OF ENDOMORPHINS 1381
PATHOPHYSIOLOGICAL IMPLICATIONS OF ENDOMORPHINS 1382
CONCLUSION 1383
Acknowledgments 1383
References 1383
186: Casomorphins and Hemorphins—Opioid Active Peptides Released by Partial Hydrolysis of Structural Proteins 1385
ABSTRACT 1385
DISCOVERY OF THE b-CASOMORPHINS AND THE HEMORPHINS 1385
THE FORMATION OF b-CASOMORPHINS AND HEMORPHINS 1386
RECEPTOR SELECTIVITY AND ITS MODULATION 1387
BIOLOGICAL ACTIONS AND FUNCTIONAL RELEVANCE OF THE b-CASOMORPHINS AND HEMORPHINS 1387
IMPLICATIONS OF b-CASOMORPHINS AND HEMORPHINS IN PATHOPHYSIOLGY 1388
CONCLUSION 1389
Acknowledgments 1389
References 1389
187: Anti-Opioid Peptides 1391
ABSTRACT 1391
INTRODUCTION 1391
REGULATION OF OPIOID ANALGESIA BY CCK 1391
CCK GENE EXPRESSION IN RESPONSE TO OPIOID ANALGESIA 1392
CCK RELEASE IN RESPONSE TO OPIOID ANALGESIA 1393
CELLULAR AND MOLECULAR MECHANISMS FOR CCK-OPIOID INTERACTIONS 1393
REGULATION OF OPIOID ANALGESIA BY NPFF 1393
REGULATION OF OPIOID ANALGESIA BY NOCICEPTIN 1394
REGULATION OF u-OPIOID SYSTEMS BY MIF-1, TYR-MIF-1, AND TYR-W-MIF-1 1394
Acknowledgment 1395
References 1395
188: Nociceptin 1397
ABSTRACT 1397
DISCOVERY 1397
STRUCTURE OF PRECURSOR MRNA/GENE 1397
DISTRIBUTION OF MRNA AND PEPTIDE 1399
BIOSYNTHESIS AND DEGRADATION 1400
RECEPTOR 1400
BIOLOGICAL ACTIONS 1400
PATHOPHYSIOLOGICAL IMPLICATIONS 1402
References 1402
189: Role of Tachykinins in Spinal Nociceptive Mechanisms and Their Interactions with Opioids 1405
ABSTRACT 1405
DISTRIBUTION OF TACHYKININS IN DORSAL ROOT GANGLIA AND THE SPINAL CORD 1405
PLASTICITY OF THE EXPRESSION OF TACHYKININS AND THEIR RECEPTORS FOLLOWING INFLAMMATION AND NERVE INJURY 1405
RELEASE OF TACHYKININS IN THE SPINAL CORD 1406
INVOLVEMENT OF TACHYKININS IN SPINAL NOCICEPTION 1406
NK-1 RECEPTOR AND NEUROPATHIC PAIN 1406
SP-SAPORIN AND NK-1 RECEPTOR EXPRESSING LAMINAE I NEURONS IN NOCICEPTION 1407
INTERACTION BETWEEN TACHYKININS AND OPIOIDS 1407
THE FAILURE OF NK-1 ANTAGONISTS AS ANALGESICS IN HUMANS 1407
References 1408
190: Exorphin-Opioid Active Peptides of Exogenous Origin 1411
ABSTRACT 1411
OPIOID PEPTIDES DERIVED FROM PLANT PROTEINS 1411
OPIOID PEPTIDES DERIVED FROM ANIMAL PROTEINS 1412
INTRAPROTEIN OPIOID SEQUENCE 1414
CLASSIFICATION OF EXORPHINS ACCORDING TO THEIR STRUCTURE 1414
OPIOID ANTAGONIST AND ANTI-OPIOID PEPTIDE DERIVED FROM PROTEINS 1415
CONCLUSION 1416
Acknowledgments 1416
References 1416
191: Opioid-Substance P Chimeric Peptides 1419
ABSTRACT 1419
INTRODUCTION 1419
CROSS-INTERACTION OF TACHYKININ AND OPIOID SYSTEMS 1420
TACHYKININ ANTAGONIST–OPIOID AGONIST CHIMERIC COMPOUNDS 1420
TACHYKININ AGONIST–OPIOID AGONIST CHIMERIC COMPOUNDS 1421
CONCLUSION 1423
References 1423
XVIII: Neurotrophic Peptides Section 1425
192: VIP- and PACAP-Related Neuroprotection 1425
ABSTRACT 1425
DISCOVERY 1425
STRUCTURE OF THE PRECURSOR mRNA, DISTRIBUTION, AND PROCESSING 1425
VIP NEUROPROTECTION 1425
RECENT RESEARCH ON VIP: CONCENTRATING ON RECEPTORS AND MECHANISMS 1426
RECENT RESEARCH ON PACAP 1427
NAP: TREATMENT THROUGH A VIP-RELATED MECHANISM 1428
CONCLUSION 1428
Acknowledgments 1428
References 1428
193: Insulin-Like Growth Factor 1 1431
ABSTRACT 1431
DISCOVERY 1431
STRUCTURE OF PRECURSOR mRNA/GENE 1431
DISTRIBUTION OF THE mRNA 1432
PROCESSING 1433
RECEPTORS 1433
ACTIVE AND/OR SOLUTION CONFORMATION 1434
BIOLOGICAL ACTIONS 1434
PATHOPHYSIOLOGICAL IMPLICATIONS 1435
References 1436
194: Erythropoietin—A Hematopoietic Hormone with Emerging Diverse Activities 1439
ABSTRACT 1439
DISCOVERY 1439
STRUCTURE OF THE PRECURSOR Epo mRNA/GENE 1439
DISTRIBUTION OF Epo mRNA 1439
PROCESSING OF Epo 1440
THE Epo RECEPTOR 1440
Epo BIOLOGICAL ACTIONS 1440
PATHOPHYSIOLOGICAL IMPLICATIONS 1444
References 1445
195: Neuregulins 1447
ABSTRACT 1447
DISCOVERY AND STRUCTURE 1447
DISTRIBUTION AND PROCESSING 1447
RECEPTORS 1448
BIOLOGICAL ACTIONS 1449
Acknowledgments 1450
References 1451
196: The Neurotrophins 1453
ABSTRACT 1453
DISCOVERY OF NERVE GROWTH FACTOR 1453
STRUCTURE OF THE mRNA/GENE 1453
DISTRIBUTION OF THE mRNA 1453
PRECURSOR PROTEIN: PROCESSING AND ACTIVITY 1454
CONFORMATION 1454
RECEPTORS—BINDING SITES 1455
TRKA AND p75 RECEPTORS—STRUCTURE 1455
RECEPTOR SIGNALING 1456
NEUROTROPHINS—RETROGRADE TRANSPORT 1456
p75 RECEPTOR SIGNALING 1457
NEUROTROPHINS—PHYSIOLOGICAL ROLE AND ROLES IN PATHOLOGY 1457
CLINICAL PROSPECTS 1458
References 1458
XIX: Blood-Brain Barrier Peptides Section 1461
197: Amino Acid Transport Across the Blood–Brain Barrier 1461
ABSTRACT 1461
BRAIN AMINO ACID REGULATION 1461
BLOOD–BRAIN BARRIER AMINO ACID TRANSPORT 1462
TRANSPORT SYSTEMS 1462
CONCLUSION 1466
References 1467
198: Oligopeptide Transport at the Blood–Brain and Blood–CSF Barriers 1469
ABSTRACT 1469
INTRODUCTION 1469
BLOOD–BRAIN BARRIERS: GENERAL PROPERTIES 1469
OLIGOPEPTIDE TRANSPORT AT THE BBB 1470
PEPTIDASES AT THE BBB 1471
OLIGOPEPTIDE TRANSPORTERS AT THE CHOROID PLEXUS 1471
PEPTIDASES AT THE CHOROID PLEXUS 1472
PEPTIDE AND PEPTIDOMIMETIC DRUG TRANSPORT 1472
CONCLUSION 1473
Acknowledgments 1474
References 1474
199: Opiate Peptides and the Blood–Brain Barrier 1475
ABSTRACT 1475
INTRODUCTION 1475
STABILIZATION 1475
TARGETING 1476
CONCLUSION 1478
References 1478
200: Permeability of the Blood–Brain Barrier to Neurotrophic Peptides 1481
ABSTRACT 1481
INTRODUCTION 1481
METHODS TO STUDY PERMEATION OF PEPTIDES ACROSS THE BBB: IN VIVO AND IN VITRO MODELS 1481
BINDING PROTEINS THAT AFFECT THE STABILITY AND PERMEATION KINETICS: INTRAVENOUS DELIVERY VERSUS IN SITU BRAIN PERFUSION 1482
PRESENCE OF RECEPTORS AT THE APICAL OR BASOLATERAL SURFACE OF THE BBB: USEFUL OR NOT FOR PEPTIDE TRANSPORT? 1483
ADSORPTIVE ENDOCYTOSIS AND CHEMICAL MODIFICATIONS THAT ENHANCE DELIVERY ACROSS THE BBB 1483
THE INTRACELLULAR TRAFFICKING OF PEPTIDES THAT LEADS TO EXOCYTOSIS 1483
SPECIFIC EXAMPLES OF THE PHARMACOKINETICS OF BBB PERMEATION 1484
THE SITUATION OF THE PARTIALLY DISRUPTED BBB AND SELECTIVE REGULATION OF THE TRANSPORT SYSTEM IN PATHOPHYSIOLOGY 1484
ENHANCED DELIVERY OF NEUROTROPHIC PEPTIDES: HOW IT AFFECTS NEUROREGENERATION 1485
CONCLUSION 1485
Acknowledgment 1485
References 1485
201: Transport of Basic Peptides at the Blood–Brain Barrier 1489
ABSTRACT 1489
INTRODUCTION 1489
bFGF 1490
TRANSPORT MECHANISM 1492
PEPTIDE DELIVERY TO THE BRAIN VIA ADSORPTIVE-MEDIATED TRANSPORT 1492
CONCLUSION 1492
Acknowledgments 1492
References 1493
202: Fibroblast Growth Factor and the Blood–Brain Barrier 1495
ABSTRACT 1495
INTRODUCTION 1495
FGF-INDUCED PROTECTION OF CEREBRAL ENDOTHELIUM AND NEURONS 1496
FGF1 AND FGF2 TRANSPORT ACROSS THE BLOOD–BRAIN BARRIER 1496
FGF SECRETION BY MICROVASCULAR ENDOTHELIAL CELLS 1497
FGF MODULATION OF CEREBRAL ENDOTHELIAL CELLS 1497
FGF2 TRANSPORT AND REGULATORY PHENOMENA AT THE CHOROID PLEXUS 1497
THE CSF-EPENDYMAL-BRAIN INTERFACE 1498
MODELING OF PEPTIDE REGULATORY SYSTEMS: INTEGRATING MULTIPLE LIGANDS AND TRANSPORT INTERFACES 1498
CONCLUSION 1499
References 1499
203: Ingestive Peptides and the Blood–Brain Barrier 1501
ABSTRACT 1501
INTRODUCTION 1501
INSULIN 1501
LEPTIN 1502
GHRELIN 1503
OTHER INGESTIVE PEPTIDES AND PROTEINS: SPECIAL INTERACTIONS WITH THE BBB 1503
CONCLUSION 1504
References 1505
204: Functional Aspects of Vasoactive Peptides at the Blood–Brain Barrier 1507
ABSTRACT 1507
ANGIOTENSIN 1507
BRADYKININ 1508
INTERPLAY BETWEEN ANGIOTENSIN AND BRADYKININ 1509
SUBSTANCE P 1509
ATRIAL NATRIURETIC PEPTIDE 1510
ENDOTHELINS 1510
ADRENOMEDULLIN 1511
MISCELLANEOUS PEPTIDES WITH VASOACTIVE PROPERTIES IN THE CNS 1511
References 1512
205: Hypothalamic Neuropeptides and the Blood–Brain Barrier 1515
ABSTRACT 1515
INTRODUCTION 1515
THE CIRCUMVENTRICULAR ORGANS 1515
TRH 1516
GnRH 1516
CORTICOTROPIN-RELEASING HORMONE 1517
VASOPRESSIN (ANTIDIURETIC HORMONE) 1517
OXYTOCIN 1518
SOMATOSTATIN 1518
PACAP 1518
References 1518
206: Diseases Mediated by the BBB: From Alzheimer’s to Obesity 1521
ABSTRACT 1521
INTRODUCTION 1521
LEPTIN AND OBESITY 1521
AMYLOID b PROTEIN EFFLUX AND ALZHEIMER’S DISEASE 1522
METHIONINE ENKEPHALIN AND ALCOHOL WITHDRAWAL 1523
GLUT-1 DEFICIENCY SYNDROME 1523
INSULIN RESISTANCE IN SEPSIS 1524
CONCLUSION 1524
References 1524
XX: Other Peptide Topics 1527
207: Prebiotic Peptides 1527
ABSTRACT 1527
INTRODUCTION 1527
THE PRIMITIVE EARTH SCENARIO 1527
THE FORMATION OF AMINO ACIDS 1528
THE FORMATION OF PEPTIDES 1528
A PEPTIDE WORLD AS THE ORIGIN OF LIFE? 1530
References 1531
208: Mixture-Based Combinatorial Libraries 1533
ABSTRACT 1533
INTRODUCTION 1533
GENERAL METHODS 1533
m-RECEPTOR LIGANDS 1535
d-RECEPTOR LIGANDS 1536
k-RECEPTOR LIGANDS 1536
m-, d-, AND k-LIGANDS 1536
ORPHAN RECEPTOR LIGANDS 1536
TESTING MIXTURES IN VIVO 1537
CONCLUSION 1537
FUTURE STUDIES 1538
References 1538
209: Use of Synthetic Peptides for Structural and Functional Analyses of Viruses Like HIV 1541
ABSTRACT 1541
INTRODUCTION 1541
HIV-1-DERIVED SYNTHETIC PEPTIDES 1541
THE HIV-1-SPECIFIC VIRUS PROTEIN U 1542
STRUCTURE AND FUNCTION OF THE LENTIVIRAL PROTEIN R 1543
THE TRANS-ACTIVATOR OF TRANSCRIPTION (Tat) OF HIV-1 1544
THE HIV-1 PROTEASE 1545
THE HIV-1 p6 Gag PROTEIN 1546
THE HIV-1 Gag PROTEINS NC AND MA 1547
CONCLUSION 1547
Acknowledgments 1548
References 1548
210: Pheromone Peptides 1551
ABSTRACT 1551
INTRODUCTION 1551
BACTERIAL PHEROMONE PEPTIDES 1552
FUNGAL PHEROMONE PEPTIDES 1552
ARTHROPOD PHEROMONE PEPTIDES 1555
ANNELID PHEROMONE PEPTIDES 1556
MOLLUSK PHEROMONE PEPTIDES 1556
VERTEBRATE PHEROMONE PEPTIDES 1556
CONCLUSION 1557
References 1557
211: Fish Peptides 1561
ABSTRACT 1561
INTRODUCTION 1561
MELANIN-CONCENTRATING HORMONE 1561
UROTENSINS 1562
ADRENOMEDULLIN 2/INTERMEDIN 1562
STANNIOCALCINS 1563
CONCLUSION 1564
References 1564
212: Peptides and Sleep 1567
ABSTRACT 1567
INTRODUCTION 1567
HYPOTHALAMIC-PITUITARY-SOMATOTROPIC SYSTEM 1567
HYPOTHALAMIC-PITUITARYADRENOCORTICAL SYSTEM 1569
ACTH 1569
HYPOTHALAMIC-PITUITARY-THYROID SYSTEM 1570
OTHER PEPTIDES 1570
CONCLUSION 1571
Acknowledgment 1572
References 1572
213: Peptide Chronomics 1575
ABSTRACT 1575
PREAMBLE 1575
INTRODUCTION 1575
AVOIDING BLUNDERS 1578
CHRONOMICS SPAWNED BY CHRONOBIOLOGY MAPS DYNAMICS 1581
END POINTS 1581
SUSCEPTIBILITY RHYTHMS 1588
ATLAS 1588
BEGINNINGS OF OPPORTUNISTIC MAPPING ALONG THE SCALE OF YEARS 1588
MAPS OF PEPTIDES IN MEN 1593
PEPTIDE CHRONOMICS IN WOMEN 1593
BREAST CANCER RISK ASSESSMENT 1599
PROSTATE CANCER RISK ASSESSMENT 1599
DISCUSSION 1602
CONCLUSION 1603
Acknowledgments 1607
References 1607
Index 1611
Color Plates 1643