Orphan G Protein-coupled Receptors and Novel Neuropeptides

by Civelli, Olivier; Zhou, Qun-yong

• ISBN13: 9783540783503
• ISBN10: 3540783504
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-08-03
• Publisher: Springer Verlag

Summary

"Over the last decade it has been shown that orphan G protein-coupled receptors (GPCRs) can be used as targets to discover novel neuropeptides. A dozen neuropeptides have been identified through this approach. Each of these neuropeptides has opened new doors for our understanding of fundamental physiological or behavioral responses. The chapters in this book review the latest research in the field, most of them are written by the original discoverers of the respective novel neuropeptide. Emphasis is set not only on their discovery but also on their functional significance."--BOOK JACKET.

Table of Contents

The Orphanin FQ/Nociceptin (OFQ/N) System	p. 1
Discovery of OFQ/N	p. 1
Pharmacology and Cellular Responses Induced by OFQ/N	p. 2
Synthesis and Inactivation of OFQ/N	p. 3
The OFQ/N and Opioid Systems	p. 4
Tissue Distribution of the OFQ/N System	p. 6
The Functional Implications of the OFQ/N System	p. 8
Locomotion	p. 8
Pain	p. 9
Drug Dependence	p. 10
Anxiety and Stress	p. 11
Learning and Memory	p. 12
Depression	p. 12
Seizures	p. 13
Food Intake	p. 13
Cardiovascular and Renal Systems	p. 14
Cough and Bronchial Constriction	p. 14
Immune System	p. 15
Conclusions	p. 15
References	p. 17
Orexins and Orexin Receptors: From Molecules to Integrative Physiology	p. 27
Introduction	p. 27
Orexin and Orexin Receptors	p. 28
Identification of Orexin (Hypocretin) by Deorphaning of Two GPCRs	p. 28
Orexin Receptors	p. 29
Distribution of Orexin Neurons	p. 29
Distributions of Orexin Receptors	p. 30
Neural Circuits of Orexin Neurons	p. 30
Neuronal Afferents	p. 30
Local Interneurons	p. 32
Efferents of Orexin Neurons	p. 32
Roles of Orexins in Regulation of Sleep/Wake States	p. 32
Interaction with Sleep and Arousal Centers	p. 32
Interaction with Waking Centers	p. 35
Roles of Orexins in Feeding Behavior	p. 37
Interaction with Hypothalamic Neurons	p. 37
Regulation of Orexin Neurons by Humoral Factors	p. 38
Mechanism of Orexin-mediated Feeding	p. 38
Orexin as Effector of Food Entrainable Oscillator (FEO)	p. 39
Roles of Orexins in Reward Systems	p. 41
Input from Reward Systems	p. 41
Output to Reward Systems	p. 41
Orexins in Emotion, Stress Responses and Autonomic Nervous System	p. 42
Input from Mesolimbic System	p. 42
Stress Response	p. 44
Orexin in Autonomic Nervous System	p. 44
Clinical Implications	p. 45
Orexin Deficiency and Narcolepsy-Cataplexy	p. 45
Orexin Agonists	p. 45
Orexin Antagonists	p. 47
Conclusion	p. 48
References	p. 48
Prolactin-Releasing Peptide	p. 57
Molecular Pharmacology	p. 57
PrRP	p. 57
PrRP Receptor	p. 59
Anatomical Distribution	p. 62
PrRP	p. 62
PrRP Receptor	p. 63
Comparison Between PrRP and PrRP Receptor Expression	p. 65
Functional Implications	p. 69
Prolactin Release	p. 70
Stress and Anxiety Response	p. 70
Food Intake and Energy Homeostasis	p. 72
Pain Processing	p. 73
Sexual and Reproductive Functions	p. 74
Sleep and Arousal	p. 75
Pressor Effects	p. 76
Other Actions	p. 77
Conclusion	p. 78
References	p. 79
Structure and Function of Ghrelin	p. 89
Introduction	p. 89
Discovery and Structure Determination of Ghrelin	p. 90
Des-Acyl Ghrelin	p. 91
Ghrelin Gene and the Structure of the Ghrelin Precursor	p. 93
Enzyme for Acyl-Modification of Ghrelin	p. 93
Ghrelin Receptor Family	p. 94
Ghrelin and Motilin	p. 95
Distribution of Ghrelin	p. 96
Plasma Ghrelin	p. 96
Gastric and Intestinal Ghrelin	p. 96
Pancreatic Ghrelin	p. 98
Pituitary Ghrelin	p. 99
Ghrelin in the Brain	p. 99
Physiological Functions of Ghrelin	p. 99
Growth Hormone Releasing Activity of Ghrelin	p. 100
Appetite Stimulating Activity of Ghrelin	p. 101
Pathway of the Ghrelin Signal; from Peripheral Tissues to the Central Nervous System	p. 103
Ghrelin and Eating Disorders	p. 104
Cardiovascular Function of Ghrelin	p. 105
Gastrointestinal Function of Ghrelin	p. 105
Ghrelin and Pancreatic Function	p. 106
Ghrelin and the Process of Learning and Memory	p. 106
Obestatin, a Ghrelin Precursor-Derived Peptide?	p. 107
Epilogue	p. 108
References	p. 108
GPR54 and Kisspeptins	p. 117
Introduction	p. 117
The GPR54 Receptor	p. 119
Kiss1	p. 119
Role in Metastasis	p. 121
Role in Reproduction	p. 122
GPR54 Mutations in Hypogonadotropic Hypogonadism	p. 122
Hypothalamic Expression Pattern	p. 124
Stimulation of Gonadotropin Secretion	p. 126
Activation at Puberty	p. 128
Kiss1 Regulation by Sex Steroids	p. 129
Kissl Expression During the Estrus Cycle	p. 131
Seasonal Breeding	p. 132
Lactation	p. 133
Kisspeptin Action at Non-Hypothalamic Sites	p. 133
Pituitary	p. 133
Metabolism	p. 134
Ovary/Testes	p. 136
Placenta	p. 136
References	p. 137
Neuropeptide S: Anatomy, Pharmacology, Genetics and Physiological Functions	p. 145
Identification and Structure of NPS	p. 145
Anatomyand Neurochemistry of the NPS System	p. 147
Pharmacology and Genetics of NPSR	p. 148
Modulation of Arousal and Wakefulness by NPS	p. 150
Anxiolytic-Like Effects of NPS	p. 151
Modulation of Feeding Behavior by NPS	p. 152
The NPS System as Part of Neural Networks	p. 153
Conclusions	p. 154
References	p. 155
The Melanin-Concentrating Hormone System and Its Physiological Functions	p. 159
Introduction: MCH from Fish Scales	p. 159
MCH Gene and Its Primary Functions in Mammals	p. 161
MCH Receptors and Receptor Signaling	p. 164
Discovery of MCH Receptor Through Orphan Receptor Strategies	p. 164
Characterization of the MCH1R-Signaling Pathway	p. 167
Effects of MCH1R Antagonism on Physiological Responses	p. 169
Efficacy of Feeding Behavior and Energy Balance	p. 169
Efficacy in Anxiety, Depression, and Stress	p. 170
Peripheral Roles of the MCH-MCH Receptor System	p. 171
Conclusions	p. 173
References	p. 173
Biological Function of Prokineticins	p. 181
Introduction	p. 181
Distribution of Prokineticin Receptors	p. 182
Regulatory Function of PK2 in Circadian Rhythms	p. 182
Function of PK2 in Neurogenesis	p. 186
Functions in Angiogenesis	p. 188
Functions in the Reproductive System	p. 189
Prokineticins as Regulators of Gastrointestinal Motility	p. 191
Prokineticins and Pain Perception	p. 192
Role of Prokineticins in the Development and Function of Blood Cells	p. 193
Summary and Perspectives	p. 194
References	p. 194
Neuromedin S: Discovery and Functions	p. 201
Discovery of Neuromedin S	p. 201
Structure of Neuromedin S	p. 203
Receptors for Neuromedin S	p. 204
Distribution of Neuromedin S	p. 204
Functions of Neuromedin S	p. 205
Circadian Oscillator System	p. 206
Feeding Regulation	p. 207
Gonadotropic Axis	p. 208
Antidiuretic Action	p. 209
Summary	p. 209
References	p. 210
Relaxin-3, INSL5, and Their Receptors	p. 213
Insulin Peptide Superfamily	p. 214
Is LGR7 the Physiological Receptor for R3?	p. 216
GPCR135 is Likely the Physiological Receptor for R3	p. 216
GPCR135 and R3 are Highly Conserved Across Species	p. 218
Is There an Additional Receptor for R3?	p. 218
Does GPCR142 Play a Significant Role in Higher Species?	p. 221
Is There an Additional Ligand for GPCR142?	p. 221
INSL5 Is Likely the Endogenous Receptor for GPCR142	p. 223
Insulin Family of Peptides Activate Three Different Classes of Receptors	p. 223
Relaxin-3, the Ancestor Gene for the Relaxin Subfamily of Peptides	p. 225
Creation of Selective Pharmacological Tools for GPCR135 In Vivo Studies	p. 226
R3/I5 Chimeric Peptides as a Selective Agonist for GPCR135 and GPCR142 over LGR7	p. 226
R3 Chimeric Peptide Studies Shed Light on the Mechanism of the Ligand/Receptor Interactions Between Relaxin-Related Peptides and Their Receptors	p. 228
[125I]R3/I5 Is a Valuable Tool for Mapping GPCR135 Binding Sites in the Brain	p. 228
R3(B¿23-27)R/I5 Is a Selective Antagonist for GPCR135 and GPCR142	p. 231
GPCR135 Selective Agonist (R3/I5) Stimulates Feeding in Rats, an Effect Blocked by Co-Administration of a GPCR135 Selective Antagonist [R3(B¿23-27)R/I5]	p. 232
Summary	p. 233
References	p. 234
The NPB/NPW Neuropeptide System and Its Role in Regulating Energy Homeostasis, Pain, and Emotion	p. 239
Introduction	p. 239
Identification of NPB and NPW	p. 240
Structures of NPB and NPW	p. 240
Structure-Activity Relationships of NPB and NPW	p. 242
Structures and Functions of NPBWR1 and NPBWR2	p. 243
Tissue Distributions of NPB/NPW and NPBWR1/NPBWR2	p. 244
Neuropeptide B	p. 244
Neuropeptide W	p. 246
NPBWR1 (GPR7)	p. 246
NPBWR2 (GPR8)	p. 247
Pharmacological Activities of NPB as NPW	p. 247
Feeding and Energy Homeostasis	p. 247
Effect on Inflammatory Pain	p. 248
Neuroendocrine Regulation	p. 249
Autonomic Regulation	p. 250
Emotion and Behavior	p. 250
Effects on Circadian Rhythm	p. 251
Peripheral Actions	p. 251
Phenotypes of NPBWR1- and NPB-Deficient Mice	p. 253
NPBWR1-Deficient Mice	p. 253
NPB-Deficient Mice	p. 253
Discussion	p. 254
References	p. 255
Subject Index	p. 257
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