Neuropeptide Y (NPY) is a ubiquitous and important messenger in the nervous system, with a wide range of physiological roles. It is involved in the body energy balance and is one of the most potent stimuli of food intake known. NPY also acts to regulate central and peripheral autonomic functions. This book, written by academic and industrial experts in the field, links the most recent basic experimental knowledge about NPY and its receptors with areas of clinical importance. This book will be of interest to those working in all areas of research affected by NPY, such as food intake and energy homeostasis, cardiovascular regulation and G-protein-coupled receptors, as well as those interested in the development of drugs as NPY targets. Key Features * The hypothalamic role of NPY and its relationship with eating disorders and diabetes * The sympathetic nervous system role of NPY and its involvement in cardiovascular disorders * Characterization of NPY receptor types and their brain distribution, molecular biology and pharmacology * Development of peptide and non-peptide receptor antagonists
Edition: 1st
Publisher: Academic Press
Year: 1996
Language: English
Commentary: 6589
Pages: 242
Front Cover......Page 1
Neuropeptide Y and Drug Development......Page 4
Copyright Page......Page 5
Contents......Page 6
Contributors......Page 9
Preface......Page 11
1.1 Multiple receptor types......Page 14
1.2 Yl receptors......Page 15
1.3 Y2 receptors......Page 16
1.5 PPl/Y receptors......Page 18
1.6 Y5 receptors......Page 23
References......Page 24
2.1 Introduction......Page 28
2.2 Pathways mediating the central effects of neuropeptide Y......Page 31
2.3 Neuropeptide Y and the regulation of feeding......Page 32
2.4 NPY and fat deposition......Page 34
2.5 NPY and pituitary function......Page 36
2.7 NPY and obesity......Page 39
2.8 NPY, bulimia and anorexia nervosa......Page 41
2.9 NPY and diabetes......Page 42
References......Page 43
3.1 Introduction......Page 54
3.3 NPY in plasma and its clearance......Page 55
3.4 NPY in sympathetic neurotransmission......Page 56
3.5 NPY and cardiovascular disorders......Page 61
References......Page 62
4.1 Introduction......Page 70
4.2 Comparative distribution of NPY receptor types......Page 72
4.3 Functional significance of various NPY receptor types......Page 83
4.4 Conclusion......Page 91
References......Page 92
5.1 Introduction......Page 100
5.2 Yl receptors......Page 102
5.3 Y2 receptors......Page 105
5.4 Pancreatic polypeptide receptors......Page 109
5.5 Discussion......Page 113
References......Page 116
6.1 Neuropeptide Y: sequence and secondary structure......Page 120
6.2 Analoguesfor the characterization of the receptor types......Page 121
6.3 Structure-activity relationships......Page 123
6.4 A model of active conformations......Page 131
References......Page 135
7.1 Background......Page 140
7.2 Design of small peptide antagonists of neuropeptide Y......Page 141
7.3 High-affinity peptide ligands......Page 148
7.4 Peptide dimers as potent NPY antagonists......Page 155
7.5 Pentapeptide dimers and multimers......Page 162
References......Page 164
8.1 Introduction......Page 170
8.2 Discovery of SR 120819A......Page 171
8.3 Biochemical profile of SR 120819A......Page 172
8.5 Pharmacological profile of SR 120819A in vivo......Page 177
8.6 Conclusion......Page 181
References......Page 183
9.1 Introduction......Page 188
9.2 The design of the Yl-receptor antagonist BIBP 3226......Page 189
9.4 The receptor binding model of BIBP 3226......Page 191
9.5 The pharmacological profile of BIBP 3226......Page 198
9.6 Conclusions......Page 201
References......Page 202
10.1 Introduction......Page 204
10.2 Design and synthesis of peptide or peptide-like NPY receptor antagonists based on the analysis of structural analogs of NPY......Page 205
10.3 Design and synthesis of non-peptide NPY receptor antagonists based on pharmacophore information derived from the analysis of peptide or peptide-like NPY receptor antagonists......Page 208
10.4 Identification of non-peptide NPY receptor antagonists through the screening of combinational libraries......Page 213
References......Page 214
Index......Page 216
List of abbreviations (for plate section)......Page 224
Color Plate Section......Page 225
