Pharmacology of GABA and glycine neurotransmission:
Saved in:
| Format: | Book |
|---|---|
| Language: | English |
| Published: |
Berlin [u.a.]
Springer
2001
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| Series: | Handbook of experimental pharmacology
150 |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXI, 413 S. Ill., graph. Darst. |
| ISBN: | 3540676163 |
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| 245 | 1 | 0 | |a Pharmacology of GABA and glycine neurotransmission |c contributors B. E. Alger ... Ed. Hanns Möhler |
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| adam_text | Contents
Section I: Physiology of the Neurotransmitters GABA and Glycine
CHAPTER 1
Physiology of the GABA and Glycine Systems
B.E. Alger and F.E.N. Le Beau. With 8 Figures 3
A. Introduction 3
B. Subtypes of Interneurons 4
I. Electrophysiological Properties of Interneurons 5
1. Voltage Dependent Channels 6
2. Ligand Gated Channels 8
C. Physiological Responses Mediated by Inhibitory
Neurotransmitters 10
I. Membrane Effects of GABA and Glycine 10
II. Depolarizing GABA and Glycine Responses 12
1. Depolarizing GABA and Glycine Responses
in Young Tissue 12
2. Depolarizing GABAA Responses in Adult Tissue 13
III. Membrane Potential Changes Caused by GABA in
Unimpaled Cells 14
D. Miniature Inhibitory Postsynaptic Currents 15
I. Saturation of Receptor Patches by Quantal Release 15
II. Co Release of GABA and Other Transmitters 19
1. GABA and Glycine 19
2. Co Release of GABA and ATP 19
III. Multiquantal Release 20
IV. Tonic Inhibition 23
E. Dendritic Inhibition 24
I. Control of Dendritic Electroresponsiveness 24
II. Dendrodendritic Inhibition 25
III. Back Propagating Action Potentials 26
IV. Control of Persistent Cation Currents 28
XII Contents
F. Somatic Axonal Inhibition 28
I. Conduction Block Along the Preterminal Axon 28
II. Depolarization Induced Suppression of
Inhibition (DSI) 30
III. Autoreception and Inhibition 33
1. Autaptic Transmission 33
2. Preterminal Extrasynaptic Receptors 33
G. GABAB Responses 34
I. Postsynaptic Inhibition 34
II. Presynaptic Inhibition 36
1. GABAB Autoreceptor Activation 36
2. Mechanism of Presynaptic GABAB Inhibition 37
III. GABAB Enhancement of Synaptic Activity 38
H. Response Plasticity and IPSPs 39
I. Short Term Plasticity of Interneuron Output 39
II. Balance Between Excitation and Inhibition 41
III. The Roles of IPSPs in Regulating Plasticity at
Excitatory Synapses 42
1. LTD of GABAAergic IPSPs in Hippocampus 42
2. LTD of GABAAergic IPSPs in Cerebellum 43
IV. Long Lasting Enhancement of GABAA IPSPs 45
1. LTP of GABAAergic IPSPs 45
2. LTP of Glycinergic IPSPs 46
3. Long Lasting Enhancement of IPSPs Not LTP 47
V. Target Cell Specificity of Action 47
VI. Facilitation of LTD Induction at Other Synapses
by IPSP Depression 48
I. Synaptic Inhibition and the Generation of Rhythmic Firing
Patterns in Populations of Cells 49
I. Gamma Oscillations 50
II. Theta Rhythms 51
III. Single Unit Studies In Vivo 51
IV. Thalamic Rhythms 52
V. Depolarizing GABAA Responses and Rhythmic Firing .... 53
VI. Hypersynchrony and Pathology 54
VII. Control of Rhythmic Firing Through Inhibition of
Gap Junctional Connections 55
J. The Role of Inhibition in Sensory Processing 56
I. Receptive Field Shape 56
II. Dynamic Modulation of Receptive Fields 57
1. Deafferentation Plasticity 57
2. Activity Dependent Receptive Field Modifications 58
3. Glycine and Motor Reorganization 59
K. Conclusions 60
References 60
Contents XIII
Section II: Pharmacology of the GABA System
GABAA Receptors
CHAPTER 2
The Molecular Architecture of GABAA Receptors
E.A. Barnard. With 2 Figures 79
A. Repertoire of Subunit Types 79
I. Structural Diversity and Uniformity 79
II. Subfamilies of Subunits 82
B. The Subunit Number per Receptor Molecule 83
C. Subunits Within the Pentamer 84
I. Two Subunit Pools for Receptor Assembly 84
II. A Constrained Combinatorial System for the
Receptor Compositions 85
D. Stoichiometry Within the Pentamer 88
I. Co occurrence of Two Isoforms of One Subunit Type 88
II. Possibilities for Subunit Stoichiometry 89
E. GABAA Receptors Containing Other Types of Subunits 89
I. The 8 Subunit 90
II. The e Subunit 90
III. The n Subunit 91
IV. The 9 Subunit 91
F. The p Subunits 91
G. Conclusions on the Subtypes 92
References 94
CHAPTER 3
Functions of GABAA Receptors: Pharmacology and Pathophysiology
H. Mohler. With 3 Figures 101
A. Introduction 101
B. Pharmacology of GABAA Receptor Subtypes 101
I. Benzodiazepine Actions at GABAA Receptor
Subtypes 101
1. Distinction of Receptor Subtypes by Point Mutations ... 101
2. Sedation and Receptor Subtypes 103
3. Amnesia and Receptor Subtypes 103
4. Anticonvulsant Activity and Receptor Subtypes 104
5. Myorelaxation, Potentiation and Receptor
Subtypes 104
6. Anxiolytic Activity and Receptor Subtypes 104
7. Strategies for Drug Design 105
II. Ethanol and GABAA Receptor Subtypes 105
III. Anaesthetics and Pentobarbital 106
I
XIV Contents
C. GABAA Receptor Mutants as Models for Disease 106
I. Anxiety Behaviour and Bias for Threat Cues 106
1. Genetically Defined Animal Model of Anxiety 107
2. Enhanced Reactivity to Natural Aversive Stimuli 107
3. Learned Aversive Stimuli 108
4. Pathophysiology of Anxiety Disorders 108
II. Craniofacial Development 110
III. Angelman s Syndrome 110
IV. Desynchrony of Neuronal Oscillations 110
D. Limitations of the Gene Inactivation Approach 110
I. Adaptation Ill
II. Severity of Impairment Ill
III. Marker Genes Ill
IV. Strain Differences 112
References 112
CHAPTER 4
Steroid Modulation of GABAA Receptors
J.J. Lambert, J.A. Peters, S.C. Harney, and D. Belelli.
With 2 Figures 117
A. Introduction 117
B. Structure Activity Relationship for Steroids at
the GABAA Receptor 120
I. Enantioselectivity of Steroid Action 122
II. The Ring System 122
III. C2 Substitution 122
IV. C3 Substitution 124
V. C5, C10 or Cll Substitution 126
VI. The C17 Side Chain 126
VII. C20 Substitution 127
VIII. C21 Substitution 127
IX. Summary 127
C. Neurosteroid Binding Site Heterogeneity and the Influence
of GABAA Receptor Subunit Composition upon Neurosteroid
Action 128
I. a Subunits 128
II. P Subunits 130
III. ySubunits 130
IV. The 8 Subunit 130
V. The £ Subunit 130
VI. Summary 131
D. Molecular Mechanism of Neurosteroid Action 131
E. Neurosteroid Effects on Synaptic Transmission 132
Contents XV
F. Concluding Remarks 134
References 135
CHAPTER 5
Allosteric Modulation of GABAA Receptor Function by
General Anesthetics and Alcohols
M.D. Krasowski, R.A. Harris, and N.L. Harrison.
With 5 Figures 141
A. Introduction 141
B. What is a General Anesthetic? 141
C. Special Considerations for Alcohol 143
D. Overview of Ligand Gated Ion Channels 143
E. GABAA and Glycine Receptors 144
F. Pharmacological Criteria for a Reasonable General Anesthetic/
Alcohol Target Site 146
I. What is the Clinically Relevant Concentration for a
General Anesthetic? 147
II. Anatomical Location 148
III. Stereoselectivity 148
IV. Hydrophobicity 150
V. Alcohol Cutoff 150
G. Experimental Approaches to Studying General Anesthetic
and Alcohol Actions at the GABAA Receptors 151
H. Actions of General Anesthetics at GABAA Receptors 152
I. Volatile Anesthetics and Anesthetic Gases 155
J. Intravenous Anesthetic Agents 157
K. Alcohols 158
L. GABAA and Glycine Receptors and Ethanol Action 158
M. Cutoff 160
N. Discussion and Future Directions 161
References 162
CHAPTER 6
Anticonvulsants Acting on the GABA System
B.S. Meldrum and P. Whiting. With 3 Figures 173
A. Introduction 173
I. Role of GABA and GABA Receptors in Epilepsy 173
1. Developmental Changes in GABAA
Receptor Effects 174
II. Mechanism of Action of Antiepileptic Drugs 175
B. GABA Transporters and Tiagabine 175
XVI Contents
I. Effects of Other Anti Epileptic Drugs on
GABA Transporters 178
II. Changes in GABA Transporters in Epilepsy 179
C. Vigabatrin and Inhibition of GABA Transaminase 179
D. Anticonvulsants Acting Through the GABAA Receptor 180
I. Benzodiazepines 181
II. Barbiturates 181
III. Steroids 182
IV. Loreclezole 182
V. Topiramate 183
VI. Chlormethiazole 183
E. Alterations in GABA Receptors in Epilepsy 183
I. Alterations in the Expression of GABAA Receptors in
Animal Models of Seizure 183
II. GABAA Receptors and Absence Epilepsy 186
III. Alterations in GABA Levels and GABAA Receptors
in Human Epilepsy 187
F. GABAergic Agents in Status Epilepticus 187
G. Conclusions: Future Prospects for Anti Epileptic Drugs Acting
on GABAergic Transmission 188
References 188
CHAPTER 7
Heterologous Regulation of GABAA Receptors:
Protein Phosphorylation
T.G. Smart, P. Thomas, N.J. Brandon, and S.J. Moss.
With 4 Figures 195
A. Introduction 195
B. Physiological Role of GABAA Receptors 196
C. Molecular Structure of GABAA Receptors 196
I. GABAA Receptor Subunit Families 196
II. Domain Structures and Alternative Splicing 197
III. Subunit Heterogeneity and Co Assembly 198
D. Consensus Sites for Protein Phosphorylation 198
E. Identifying Phosphorylation Sites Within GABAA Receptor
Subunits 199
I. Phosphorylation of Neuronal GABAA Receptors 199
II. Consensus Phosphorylation Sites in the Large Intracellular
Domains 200
III. Phosphorylation of Recombinant GABAA Receptors 201
1. Use of Fusion Proteins 201
2. Use of Receptor Subunits 201
F. GABAA Receptor Phosphorylation: Consequences for
Ion Channel Function 202
Contents XVII
I. cAMP Dependent Protein Kinase 202
1. Native Neurones 202
2. Recombinant Receptors 203
II. cGMP Dependent Protein Kinase 207
III. Ca27Phospholipid Dependent Protein Kinase 207
IV. Ca27Calmodulin Dependent Protein Kinase II and
Ca2+ Dependent Phosphatases 210
V. Tyrosine Kinases 212
1. GABAA Receptor: Response Rundown and Washout ... 213
G. Regulation of GABAA Receptor Cell Surface Expression 214
H. Conclusion 217
References 218
CHAPTER 8
Tolerance and Dependence to Ligands of the Benzodiazepine
Recognition Sites Expressed by GABAA Receptors
E. Costa, J. Auta, and A. Guidotti. With 2 Figures 227
A. A Mechanistic Hypothesis on the Tolerance and Dependence
to the Ligands of Benzodiazepine Recognition Sites (BZ RS)
Expressed by GABAA Receptors 227
B. Tools to study changes in GABAA receptor subunit assembly .... 228
C. Limitations in Interpreting Studies of GABAA Receptor
Chimerae With and Without Single Amino Acid Mutations 229
D. Characterization of BZ RS Ligands Endowed with Anxiolytic
and Anticonvulsant Actions 230
E. Can the Subunit Expression Modification Associated with
BZ Tolerance Explain the Decreased Intrinsic Activity of
Full Positive Allosteric Modulators at GABAA Receptors? 235
I. Changes in GABA Receptor Subunit Assembly 235
1. Studies on Ligand Binding to BZ RS 235
2. Changes in GABAA Receptor Subunit mRNA
Expression 236
3. Changes in GABAA Receptor Subunit Expression 238
II. GABAA Receptor Subunit Allosteric Uncoupling 239
F. Are Changes in GABAA Receptor Subunit Assembly
Relevant to BZ Dependence? 240
G. Development of Tolerance and Dependence Liability After
Long Term Treatment with Selective Positive Allosteric
Modulators of GABAA Receptors 242
I. Zolpidem 242
II. Abecarnil 242
H. Lack of Tolerance or Dependence Following Long Term
Treatment with Partial Positive Allosteric BZ RS Ligands 243
XVIII Contents
I. Imidazenil is Devoid of Tolerance and Dependence
Liability in Rodents 244
II. Imidazenil is Devoid of Tolerance and Dependence
Liability in Monkeys 245
References 247
CHAPTER 9
GABAA Receptors and Disease
H.Y. Kim and R.W. Olsen 251
A. Introduction 251
B. Diseases of Development and GABAA Receptors 252
C. Diseases of Adult and GABAA Receptors 254
I. GABAA Receptor Function in Adult Epilepsy 254
II. GABAA Receptor Function in Anxiety 257
III. GABAA Receptor Function in Alcoholism 258
D. Conclusion 260
References 261
CHAPTER 10
GABAC Receptors: Structure, Function and Pharmacology
J. Bormann and A. Feigenspan. With 7 Figures 271
A. Introduction 271
B. Structure of GABAC Receptors 272
I. Cloning of Vertebrate p Subunits 272
II. Subunit Composition of GABAC Receptors 272
C. Neuronal Localization 272
D. Functional Properties of GABAC Receptors 274
I. Identification of GABAC Receptors 274
II. GABA Affinity and Ion Selectivity 274
III. Single Channel Characteristics 276
IV. Pore Size 276
V. Desensitization 277
E. Pharmacology 278
I. GABAC Agonists 278
II. GABAc Antagonists 280
F. Modulation of GABAC Receptors 283
I. Extracellular Modulation 283
II. Intracellular Modulation by Protein Kinases 284
G. Physiological Function of GABAC Receptors 287
H. Terminology for GABAC Receptors 290
I. Conclusions 290
References 291
Contents XIX
GABAB Receptors
CHAPTER 11
Structure of GABAB Receptors
B. Bettler and K. Kaupmann. With 2 Figures 299
A. Physiological Evidence for GABAB Receptor Subtypes 299
B. Pharmacology, Structure and Distribution of Cloned
GABAB Receptors 300
I. Cloned GABAB Receptors 300
II. Binding Pharmacology 302
III. Molecular Determinants of Ligand Binding 302
C. Functional Studies with Recombinant GABAB Receptors 303
I. Individually Expressed BR1 and BR2 Receptors 303
II. Heteromeric BR1 + BR2 Receptors 305
D. Temporal and Spatial Distribution of Cloned GABAB
Receptors 306
E. Concluding Remarks and Future Directions 307
References 307
CHAPTER 12
Pharmacology of GABAB Receptors
N.G. Bowery 311
A. Introduction 311
B. Physiological Role 312
C. GABAB Receptor Distribution and Localization in CNS 313
D. GABAB Receptor Coupling to Adenylate Cyclase 314
E. Ca and K+ Channel Coupling to GABAB Sites 315
F. Pharmacological Effects GABAB Receptor Agonists 316
G. Pharmacological Effects GABAB Receptor Antagonists 319
H. Subtypes of Receptor 321
References 321
CHAPTER 13
GABAB Receptor Signaling Pathways
S.J. Enna. With 3 Figures 329
A. Introduction 329
B. Second Messenger Production 330
I. Overview 330
II. cAMP 330
III. Gene Transcription 334
C. Calcium Channels 336
D. Potassium Channels 337
I
XX Contents
E. Conclusion 338
References 339
GABA Transporters
CHAPTER 14
Structure and Function of GABA Transporters
B.I. Kanner 345
A. Introduction 345
B. Stoichiometry 346
C. Reconstitution and Purification 346
D. Biochemical Characterisation of the GABA Transporter 347
E. A New Superfamily of Na Dependent Neurotransmitter
Transporters 348
F. Topology 348
G. Structure Function Relationships 349
H. Conclusions 351
References 352
CHAPTER 15
Pharmacology of GABA Transporters
J.E. Clark and W.A. Clark. With 4 Figures 355
A. Introduction 355
B. Physiological Relevance of GABA Transporters 356
C. Neuronal and Glial Specific GABA Transport Inhibitors 357
D. GABA Transporter Heterogeneity 359
E. Lipophilic GABA Transport Inhibitors 361
I. THPO 361
II. Prodrugs of Nipecotic Acid, Hydroxynipecotic Acid,
and Isoguvacine 361
III. Nipecotic Acid and Guvacine Derivatives 362
F. Specific GABA Transport Inhibitors 364
I. Compounds Selective for GAT 1 364
II. Compounds Selective for GAT 2, GAT 3, and BGT 1 365
G. GABA Uptake Inhibitors as Experimental Tools 366
I. GABA Transport Inhibition and Sleep 366
II. Depolarizing Effects of GABA and Inhibition of
GABA Uptake 367
H. Conclusion 367
References 368
Contents XXI
Section III: Pharmacology of the Glycine System
CHAPTER 16
Structures, Diversity and Pharmacology of Glycine Receptors
and Transporters
H. Betz, R.J. Harvey, and P. Schloss. With 3 Figures 375
A. Introduction 375
I. The Neurotransmitter Glycine 375
B. Structure and Diversity of Glycine Transporters 376
I. Structure of Plasma Membrane Glycine Transporters 376
II. Diversity and Regulation of Plasma Membrane
Glycine Transporters 378
III. Distribution of Plasma Membrane Glycine Transporters
and Possible Physiological Function 380
IV. The Vesicular Glycine/GABA Transporter 381
C. Structure and Diversity of Glycine Receptor Channels 382
I. GlyRs are Ligand Gated Ion Channels of the
nAChR Superfamily 382
II. Glycine Receptor Isoforms 384
III. Ligand Binding Determinants 385
IV. Ion Channel Function 387
V The Peripheral Membrane Protein Gephyrin 387
VI. Pharmacology of GlyRs 389
1. Antagonism of GlyR Function by Strychnine 389
2. Amino Acids and Piperidine Carboxylic Acid
Compounds 390
3. Picrotoxinin, Cyanotriphenylborate, and Quinolinic
Acid Derivatives 390
4. Potentiation of GlyR Function by Anesthetics, Alcohol,
and Zn2+ 391
D. Concluding Remarks 393
References 393
Subject Index 403
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV013386918 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:44:57Z |
| institution | BVB |
| isbn | 3540676163 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009132106 |
| oclc_num | 643203138 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-12 DE-188 DE-578 |
| owner_facet | DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-12 DE-188 DE-578 |
| physical | XXI, 413 S. Ill., graph. Darst. |
| publishDate | 2001 |
| publishDateSearch | 2001 |
| publishDateSort | 2001 |
| publisher | Springer |
| record_format | marc |
| series | Handbook of experimental pharmacology |
| series2 | Handbook of experimental pharmacology |
| spelling | Pharmacology of GABA and glycine neurotransmission contributors B. E. Alger ... Ed. Hanns Möhler Berlin [u.a.] Springer 2001 XXI, 413 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Handbook of experimental pharmacology 150 gamma-Aminobutyric Acid cabt Neurotransmitters cabt Aminobuttersäure gamma- (DE-588)4155919-8 gnd rswk-swf Pharmakologie (DE-588)4045687-0 gnd rswk-swf Neuropharmakologie (DE-588)4041896-0 gnd rswk-swf Neurotransmitter (DE-588)4041905-8 gnd rswk-swf Glycin (DE-588)4157727-9 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Aminobuttersäure gamma- (DE-588)4155919-8 s Neurotransmitter (DE-588)4041905-8 s Pharmakologie (DE-588)4045687-0 s DE-604 Glycin (DE-588)4157727-9 s Neuropharmakologie (DE-588)4041896-0 s Möhler, Hanns 1940- Sonstige (DE-588)1063989035 oth Alger, B. E. Sonstige oth Handbook of experimental pharmacology 150 (DE-604)BV002390716 150 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009132106&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Pharmacology of GABA and glycine neurotransmission Handbook of experimental pharmacology gamma-Aminobutyric Acid cabt Neurotransmitters cabt Aminobuttersäure gamma- (DE-588)4155919-8 gnd Pharmakologie (DE-588)4045687-0 gnd Neuropharmakologie (DE-588)4041896-0 gnd Neurotransmitter (DE-588)4041905-8 gnd Glycin (DE-588)4157727-9 gnd |
| subject_GND | (DE-588)4155919-8 (DE-588)4045687-0 (DE-588)4041896-0 (DE-588)4041905-8 (DE-588)4157727-9 (DE-588)4143413-4 |
| title | Pharmacology of GABA and glycine neurotransmission |
| title_auth | Pharmacology of GABA and glycine neurotransmission |
| title_exact_search | Pharmacology of GABA and glycine neurotransmission |
| title_full | Pharmacology of GABA and glycine neurotransmission contributors B. E. Alger ... Ed. Hanns Möhler |
| title_fullStr | Pharmacology of GABA and glycine neurotransmission contributors B. E. Alger ... Ed. Hanns Möhler |
| title_full_unstemmed | Pharmacology of GABA and glycine neurotransmission contributors B. E. Alger ... Ed. Hanns Möhler |
| title_short | Pharmacology of GABA and glycine neurotransmission |
| title_sort | pharmacology of gaba and glycine neurotransmission |
| topic | gamma-Aminobutyric Acid cabt Neurotransmitters cabt Aminobuttersäure gamma- (DE-588)4155919-8 gnd Pharmakologie (DE-588)4045687-0 gnd Neuropharmakologie (DE-588)4041896-0 gnd Neurotransmitter (DE-588)4041905-8 gnd Glycin (DE-588)4157727-9 gnd |
| topic_facet | gamma-Aminobutyric Acid Neurotransmitters Aminobuttersäure gamma- Pharmakologie Neuropharmakologie Neurotransmitter Glycin Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009132106&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV002390716 |
| work_keys_str_mv | AT mohlerhanns pharmacologyofgabaandglycineneurotransmission AT algerbe pharmacologyofgabaandglycineneurotransmission |