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GABAB receptor pharmacology : a tribute to Norman Bowery / edited by Thomas P. Blackburn. — Amsterdam ; London : Academic Press, 2010. – (63.3/A244/v.58) |
Contents
Contents
Contributors xi
Preface xv
Historical Perspective and Emergence of the GABAB Receptor
I. Introduction 2
II. GABAB Receptor Ligands 5
III. Receptor Distribution 6
IV. Allosteric Modulation 7
V. Receptor Function 8
VI. Potential Therapeutic Significance
VII. Conclusion 13
References 13
Chemistry and Pharmacology of GABAB Receptor Ligands
I. Introduction 20
II. GABAB Receptor Agonists 20
III. GABAB Receptor Partial Agonists 27
IV. Positive Modulators of GABAB Receptors 29
V. GABAB Receptor Antagonists 32
VI. Conclusion 42
Acknowledgments 43
References 44
Heterodimerization of the GABAB Receptor-implications for GPCR Signaling and Drug Discovery
I. Introduction 64
II. Identification of the GABAB Receptors 65
III. The Phylogeny of GABAB Receptors GABAB Receptors in Different Species 66
IV. Structure of GABAB Receptors 70
V. Function of the GABAB Receptor Heterodimer 73
VI. GABAB as a Model System for GPCR Dimerization 79
VII. Conclusions 83
References 85
Mechanisms of GABAB Receptor Exocytosis， Endocytosis， and Degradation
I. Introduction 94
II. Cell-Surface Trafficking of GABAB Receptors 94
III. Endocytosis of GABAB Receptors 99
IV. Degradation of GABAB Receptors 104
V. Conclusions 105
Acknowledgments 107
References 108
Functional Modulation of GABAB Receptors by Protein Kinases and Receptor Trafficking
I. Introduction 114
II. Phosphorylation of GABABR and Its Functional Modulation 115
III. Phosphorylation-Independent Desensitization of GABABRs by Protein Kinases
IV. GABABR Endocytic Sorting and the Control of Receptor Cell Surface Stability 118
V. GABABR Phosphorylation and Diseases 118
VI. Conclusion 119
Acknowledgments 120
References 120
GABAB Receptor Coupling to G-proteins and Ion Channels
I. Introduction 124
II. GABAB Receptor Structure 125
III. GABAB Receptor Protein Expression 128
IV. GABAB Receptor Effectors 129
V. Formation of a Macromolecular Signaling Heterocomplex 134
VI. GABAB Receptor-Dependent Desensitization 136
VII. Conclusion 139
References 139
GABAB Receptor-Mediated Modulation of Metabotropic Glutamate Signaling and Synaptic Plasticity in Central Neurons
I. Introduction 150
II. Synaptic Organization Around Cerebellar Purkinje Cells 151
III. Possible Ligands for GABABR in Cerebellar Purkinje Cells 152
IV. Functions of GABABR Near the Excitatory Synapses 154
V. Possible Physiological Significance of GABABR-Mediated Effects on mGluR1 Signaling 162
VI. Conclusion 167
Acknowledgments 168
References 169
GABA Transporter GATI: A Crucial Determinant of GABAB Receptor Activation in Cortical Circuits?
I. Introduction 176
II. The Plasma Membrane GABA Transporter 1 176
III. Cellular and Subcellular Localization of GABABRs and GAT1 180
IV. GABABR Activation by GABA Released from Endogenous Sources 182
V. GAT1 Activity and GABABR Activation 188
VI. Conclusions 195
Acknowledgments 196
References 197
The Roles of GABAB Receptors in Cortical Network Activity
I. Introduction 206
II. GABAB Receptors in Cortical Microcircuits 207
III. Control of Network Activity by GABAB Receptors 210
IV. Conclusion 221
References 222
GABAB Receptors: Physiological Functions and Mechanisms of Diversity
I. Introduction 232
II. Physiological Functions of GABAB Receptors 233
III. Heterogeneity of Native GABAB Responses 234
IV. Functions of the Cloned GABAB Receptor Subtypes 238
V. Additional Mechanisms of Diversity 246
VI. Conclusions 248
Acknowledgments 249
References 249
Role of GABAB Receptors in Autonomic Control of Systemic Blood Pressure
I. Introduction 258
II. Overview of Autonomic Nervous System 260
III. Distribution of GABAB Receptors in CNS Autonomic Centers 261
IV. GABAB Receptor Function in the RVLM 261
V. GABAB Function in the NTS 263
VI. GABAB Receptor Function in the Hypothalamus 267
VII. Conclusion 274
Acknowledgments 275
References 276
GABAB Receptor Agonism as a Novel Therapeutic Modality in the Treatment of Gastroesophageal Reflux Disease
I. Introduction 288
II. Underlying Pathophysiological Mechanisms of GERD 289
III. The GABAB Receptor 290
IV. GABAB Receptor Agonists as Reflux Inhibitors 295
V. Conclusions 306
Acknowledgments 307
References 307
GABAB Receptors in Reward Processes
I. Introduction 316
II. GABAB Receptor Agonists， GABAB Receptor Positive Modulators， and Reward: Effects on the Rewarding Properties of Food， Intracranial Self-Stimulation， and Drugs of Abuse 336
III. GABA Receptor Agonists versus GABAB Receptor Positive Modulators 359
IV. Conclusion 360
Acknowledgments 360
References 362
GABAB Receptors in Addiction and Its Treatment
I. Introduction 374
II. Alcohol Dependence 375
III. Cocaine 379
IV. Nicotine 384
V. Opiates 385
VI. Methamphetamine 387
VII. GHB 387
VIII. Discussion 388
IX. Conclusion 392
References 392
GABAB-GIRK2-Mediated Signaling in Down Syndrome
I. Introduction 398
II. Mouse Models of DS 399
III Evidence for Cognitive Impairment in Mouse Models of DS 400
IV. Hippocampal Deficit in DS and in DS Mouse Models 402
V. A Role of GABAB-GIRK Coupling in Hippocampal Overinhibition in DS 404
VI. Potential Evidence for GABAB-Mediated Developmental and Morphological Changes in DS 415
VII. Role of GIRK in DS Pain and Cerebellar Phenotypes 417
VIII. Conclusions 418
Acknowledgments 419
References 419
GABAB Receptors and Depression: Current Status
I. Introduction 428
II. GABAB Receptors 429
III. Role of GABAB Receptors in Animal Models of Antidepressant Action 430
IV. GABAB Receptors and Cognition 435
V. Chronic Antidepressants and GABAB Receptor Function 437
VI. GABAB Receptors and the Reward System 437
VII. GABAB-5-HT Interactions
VIII. Clinical Evidence for a Role of GABAB Receptors in Depression 439
IX. Conclusion 441
Acknowledgments 441
References 442
GABA-B Receptors in Drosophila
I. Introduction 454
II. Drosophila Model in Pharmacology 454
III. Drosophila GABA System 456
IV. Drosophila GABA-B Receptors 458
V. Conclusion 462
References 462
Index 465
Contents of Previous Volumes 485
