Understanding G Protein-coupled Receptors and their Role in the CNS (The Molecular and Cellular Neurobiology Series)

Pharmacological and molecular cloning studies have shown that the superfamily of G-protein coupled receptors (GPCRs) forms one of the largest and most diverse protein families in nature. They are involved in the modulation of almost all our bodily functions and are pivotal in the regulation and control of central nervous system function. As such, pharmacological manipulation of GPCRs has been demonstrated to be valuable in the treatment of diseases of the central nervous system, ranging from Alzhmeimer's disease to schizophrenia and continues to be a key area of investigation in the search for tomorrow's medicines. The aim of this book is to bring together, for the first time in one volume, all aspects of GPCR structure and function, with an emphasis on receptors expressed in the central nervous system. The book comprises two major parts: part one provides a detailed overview of GPCR superfamily structure and function, including reviews of the mechanisms of ligand activation and inactivation, signalling through G-proteins and downstream signal transduction pathways and effector systems. Part two focuses on individual members of each of the three subfamilies of the GPCR superfamily, providing specific information about their localization, pharmacology, physiology and disease relevance. GPCRs in the CNS is essential reading for neuroscientists, pharmacologists, biochemists, molecular biologists, physiologists and all those involved in the process of drug discovery. Contents......Page 10 List of Contributors......Page 12 List of Abbreviations......Page 16 Part 1: The GPCR superfamily......Page 22 1 GPCR superfamily and its structural characterization......Page 24 2 Transcriptional regulation of GPCR expression......Page 49 3 Structural mechanics of GPCR activation......Page 64 4 G protein structure diversity......Page 84 5 GPCR signalling through enzymatic cascades......Page 108 6 GPCR signalling through ion channels......Page 129 7 Protein regulators of GPCR function......Page 145 8 Quantitative pharmacology of GPCRs......Page 162 9 Bioinformatic mining for GPCRs......Page 179 10 Characterization of orphan GPCRs......Page 197 Part 2: Family 1 GPCRs......Page 210 11 Adenosine receptors......Page 212 12 Adrenergic receptors......Page 226 13 Cannabinoid receptors......Page 242 14 Cholecystokinin receptors......Page 263 15 Dopamine receptors......Page 285 16 Galanin receptors......Page 307 17 Histamine receptors......Page 328 18 Muscarinic receptors......Page 370 19 Neuropeptide Y receptors......Page 393 20 Opioid receptors......Page 423 21 Purinergic receptors......Page 443 22 Serotonin receptors......Page 460 23 Somatostatin receptors......Page 490 24 Tachykinin receptors......Page 504 Part 3: Family 2 GPCRs......Page 524 25 Corticotropin releasing factor receptors......Page 526 26 VIP and PACAP receptors......Page 548 Part 4: Family 3 GPCRs......Page 568 27 Calcium-sensing receptors......Page 570 28 GABA[sub(B)] receptors......Page 582 29 Metabotropic glutamate receptors......Page 607 A......Page 638 C......Page 639 D......Page 640 F......Page 641 G......Page 642 K......Page 643 N......Page 644 P......Page 645 R......Page 646 S......Page 647 V......Page 648 Z......Page 649 Colour Plates......Page 650 Pharmacological and molecular cloning studies have shown that the superfamily of G protein-coupled receptors (GPCRs) forms one of the largest and most diverse protein families in nature. They are involved in the modulation of almost all our bodily functions and are pivotal in the regulation and control of central nervous system function. As such, pharmacological manipulation of GPCRs has been demonstrated to be valuable in the treatment of diseases of the central nervous system, ranging from Alzheimer's disease to schizophrenia, and continues to be a key area of investigation in the search for tomorrow's medicines. The aim of this book is to bring together, for the first time in one volume, all aspects of GPCR structure and function, with an emphasis on receptors expressed in the central nervous system. The book divides into two major sections and starts with a detailed overview of GPCR superfamily structure and function, including reviews of the mechanisms of ligand activation and inactivation, signalling through G proteins and downstream signal transduction pathways and effector systems. The focus then shifts onto individual members of each of the three subfamilies of the GPCR superfamily, providing specific information about their localization, pharmacology, physiology and disease relevance. Understanding G Protein-coupled Receptors and their Role in the CNS is essential reading for neuroscientists, pharmacologists, biochemists, molecular biologists, physiologists and all those involved in the drug discovery process