Handbook of Neurochemistry and Molecular Neurobiology - Neurotransmitter Systems

TOC.pdf......Page 0
ATP‐Mediated Signaling in the Nervous System227......Page 2
Index457......Page 3
Structural Organization of Monoamine and Acetylcholine Neuron Systems in the Rat CNS......Page 4
2 Dopamine (DA) Neurons......Page 5
2.2 Mesostriatal DA System......Page 6
3 Noradrenaline (NA) Neurons......Page 7
3.2 Myelencephalospinal NA System......Page 8
5.1 Rapheocortical 5-HT System......Page 9
6 Histamine Neurons......Page 10
7.1 Basalocortical ACh System......Page 11
7.3 Neostriatal ACh Innervation......Page 13
8.1 Dopamine Neurons......Page 14
8.3 Serotonin Neurons......Page 15
9 Concluding Remarks: A New Image of the Neuron......Page 16
References......Page 18
Brain Neurons Partly Expressing Monoaminergic Phenotype: Distribution, Development, and Functional Significance in Norm and Pathology......Page 24
1 Introduction......Page 26
2.1.1 Hypothalamus......Page 29
2.1.2 Striatum......Page 32
2.1.3 Other Brain Regions......Page 34
2.2 Bienzymatic TH- and AADC-Expressing Neurons......Page 35
2.3 Non-MA-ergic Neurons Expressing the MA Transporters......Page 36
3.1.1 Hypothalamus......Page 38
3.1.2 Extrahypothalamic Regions......Page 42
3.2 Non-MA-ergic Neurons Expressing the MA Transporters......Page 45
4.1 Monoenzymatic Neurons Expressing TH......Page 47
4.2 Monoenzymatic Neurons Expressing AADC......Page 50
4.3 Ensembles of Monoenzymatic Neurons......Page 51
4.4 Non-MA-ergic Neurons Expressing the MA Transporters......Page 54
5 Tuberoinfundibular Neurons Partly Expressing DA-ergic Phenotype in Hyperprolactinemia......Page 55
6 Striatal Neurons Partly Expressing DA-ergic Phenotype in Parkinson's Disease......Page 56
6.1 Monoenzymatic TH-Expressing Neurons......Page 57
6.2 Monoenzymatic AADC-Expressing Neurons......Page 60
6.4 Origin, Functional Properties, and Functional Significance of Striatal Neurons Partly or Completely Expressing the DA-ergic Phenotype......Page 62
7.1 Regulation of the Partial Expression of MA-ergic Phenotype by Neural Afferents......Page 65
7.2 Paracrine Regulation of the Partial Expression of MA-ergic Phenotype by Diffusive Factors......Page 67
7.3 Hormonal Regulation of the Partial Expression of MA-ergic Phenotype......Page 68
References......Page 69
In Vivo Imaging of Neurotransmitter Systems with PET......Page 77
1 Introduction: Neurotransmitter and Neuroreceptor Systems and In Vivo Neuroimaging......Page 78
2 Positron Emission Tomography......Page 79
3 Labeling Tracers and Ligands with PET Bioisotopes......Page 81
4 Preliminary Steps in the Development of Radioligands for Human CNS Receptors......Page 84
5 Measuring Radioligand Effects in the Brain......Page 85
7 Two Approaches......Page 87
7.2 Indirect Approach: Using Radiolabeled Ligands and Drug Candidates......Page 88
8 Radioligands for Mapping Neurotransmitter Systems: Some Examples......Page 89
8.1 Dopamine Receptor and Transporter Ligands......Page 91
8.2 Serotoninergic Neurotransmission Radioligands......Page 93
8.5 Central Benzodiazepine-Binding Site Ligands......Page 95
8.7 Glutamate Neurotransmission Radioligands......Page 96
References......Page 97
Synaptic and Nonsynaptic Release of Transmitters......Page 103
1 Historical Background......Page 104
3.1 Nonsynaptic Release of Transmitter......Page 105
3.2 Spillover of Transmitters......Page 107
4.2 Uptake of Transmitters by Plasma Membrane Transporters......Page 108
4.4 Effect of Drugs on Targets Located Intrasynaptically and Extrasynaptically: Law of Mass Action......Page 109
5 Conclusions......Page 110
References......Page 111
Cholinergic Transmission......Page 114
2 Synthesis, Storage, and Release of Acetylcholine......Page 115
3 Breakdown of ACh......Page 116
5 Synaptic Versus Nonsynaptic Release of ACh......Page 117
6.4 Desensitization......Page 118
6.6 Postsynaptic Nicotinic Receptors......Page 119
6.8 Special Role of Nicotinic Receptors in Neural Plasticity......Page 120
7.1 Subunits and Subtypes......Page 121
7.2 Subcellular Action Mechanisms......Page 122
7.4 Muscarinic Receptor Functions......Page 123
References......Page 125
Molecular Genetics of Brain Noradrenergic Neurotransmission......Page 129
2.1 Ontogeny......Page 130
2.4 NE Storage and Release......Page 131
2.5 NE Receptors......Page 132
2.6.1 Reuptake......Page 133
3.1.1 Tonic Versus Phasic Excitation of NE Neurons......Page 134
4 Genetics of Noradrenergic Neurotransmission......Page 135
4.1 Tyrosine Hydroxylase......Page 136
4.2 Dopamine beta Hydroxylase......Page 137
4.3 Mono-Amine-Oxydase......Page 138
4.4 Catechol-O-Methyltransferase......Page 139
References......Page 140
Dopamine and the Dopaminergic Systems of the Brain......Page 148
1 Introduction......Page 150
2.1 Tyrosine Hydroxylase......Page 151
2.4 Estimation of Dopamine Synthesis Rate from Dopa Decarboxylase Inhibition......Page 153
3.3 Estimation of Dopamine Turnover Rate by Calculation of Metabolites/Dopamine Ratio......Page 154
4 Storage of Dopamine in Neuronal Pools......Page 155
5.1 Structure of Dopamine Transporter......Page 157
6 Dopamine Receptors......Page 158
6.2 Structure of Dopamine Receptors......Page 159
6.4 Presynaptic Dopamine Receptors......Page 160
6.6 Changes in Dopamine Receptor Sensitivity and Expression......Page 161
7.1 Action Potential Propagation-Induced Dopamine Release......Page 162
7.2 Dopamine Release Evoked by Reverse-Mode Operation of Dopamine Transporters......Page 163
8 Dopaminergic Innervations in the Central Nervous System......Page 164
9.1 Neurotoxins Used for Destruction of Dopaminergic Neurons......Page 165
10 Conclusions and Future Avenues......Page 166
References......Page 167
5-Hydroxytryptamine in the Central Nervous System......Page 170
4 The Physiology of 5-HT Neurons......Page 171
5.1 The 5-HT1 Receptor Family......Page 173
5.1.1 The 5-HT1A Receptor......Page 174
5.1.2 The 5-HT1B Receptor......Page 177
5.1.3 The 5-HT1D Receptor......Page 180
5.1.5 The 5-HT1F Receptor......Page 181
5.2.1 5‐HT2A Receptor......Page 182
5.2.2 The 5‐HT2B Receptor......Page 184
5.2.3 The 5‐HT2C Receptor......Page 185
5.3 The 5-HT3 Receptor......Page 186
5.4 The 5-HT4 Receptor......Page 188
5.5 The 5-ht5 Receptors......Page 189
5.6 The 5-HT6 Receptor......Page 191
5.7 The 5-HT7 Receptor......Page 193
6 The 5-HT Transporter (SERT)......Page 195
7 Conclusions......Page 197
References......Page 198
GABA Neurotransmission: An Overview......Page 212
2.1 GAD65 and GAD67......Page 213
2.2 GAD in Non-GABAergic Neuronal Systems......Page 214
3.1 GABA-T......Page 215
4.1 Carbonyl-Trapping Agents......Page 216
5.1 Vesicular Release......Page 217
6.1 Ionotropic Receptors......Page 218
7.1 Receptor Desensitization and GABA Diffusion......Page 219
7.3.1 Functional Implications of GABA Transport Inhibition......Page 220
References......Page 221
ATP-Mediated Signaling in the Nervous System......Page 226
1 Introduction......Page 227
2 Synthesis, Utilization, and Storage of ATP in the Nervous System......Page 228
3 The Release of ATP......Page 230
4 The Extracellular Inactivation of ATP......Page 232
5 ATP Receptors......Page 234
7 The Presynaptic Modulatory Role of ATP......Page 237
8 The Role of ATP in Glia-Neuron and Glia-Glia Signaling......Page 240
9 The Role of ATP in Sensory Transmission and in the Generation of Pain......Page 242
11 ATP as a Neuroimmunomodulator......Page 243
12 Involvement of ATP Receptors CNS Diseases and their Potential Therapeutic Exploitation......Page 244
References......Page 245
Adenosine Neuromodulation and Neuroprotection......Page 254
1.1 Adenosine as a Homeostatic Modulator......Page 255
1.2 Pharmacology and Localization of Adenosine Receptors in the Brain......Page 257
1.3 Neurotransmission and Neuromodulation - Adenosine as a Neuromodulator......Page 259
1.4 Source of Endogenous Extracellular Adenosine......Page 262
1.5 Role of A1 Receptors in the Control of Synaptic Plasticity......Page 263
1.6 A2A Receptors and Modulation of Synaptic Plasticity......Page 264
2.1 Therapeutic Opportunities to Manage Neurodegenerative Diseases Targeting the Adenosine Modulation System......Page 265
2.2 A1 Receptors as Hurls for the Development of Neuronal Dysfunction......Page 266
2.3 Role of A2A Receptors in the Control of Neurodegeneration......Page 267
2.4 A2A Receptor Antagonists as Novel Anti-Parkinsonian Drugs......Page 268
2.5 Role of A2A Receptors in Alzheimer's Disease......Page 269
3 Final Comments......Page 270
References......Page 271
Regulation of AMPA Receptors by Metabotropic Receptors and Receptor Tyrosine Kinases: Mechanisms and Physiological Roles......Page 273
1 Introduction......Page 275
2.1 AMPA Receptor Structure......Page 276
2.2 AMPA Receptors and Synaptic Plasticity......Page 279
2.3 AMPA Receptor Phosphorylation......Page 281
2.4 AMPA Receptor Trafficking......Page 282
2.4.1 Proteins that Interact with Short Forms of AMPA Receptor Subunits......Page 283
2.4.3 General AMPA Receptor Interactors: Transmembrane and Extracellular Proteins......Page 284
3.1.1 Potentiation of AMPA Receptor by mGluRs......Page 285
3.1.2.3 Cerebellar Purkinje Neurons......Page 286
3.2 Dopamine Receptors......Page 288
3.2.1 Striatum......Page 289
3.2.1.1.1 Modulation of Synaptic Transmission by Dopamine in the Dorsal Striatum......Page 290
3.2.1.2 Nucleus Accumbens......Page 291
3.2.3 Retina......Page 293
3.2.4 Regulation of AMPA Receptor Subunit Expression by Dopamine......Page 294
3.2.4.2 Effect of Drugs of Abuse on AMPA Receptor Subunit Expression......Page 295
3.3 Serotonin Receptors......Page 296
3.6 Adrenergic Receptors......Page 298
3.7.2 Somatostatin Receptors......Page 299
3.7.5 Natriuretic Peptide Receptors......Page 300
4.1 Insulin and IGF Receptors......Page 301
4.2 Neurotrophin Receptors......Page 302
4.2.1 Cultured Neocortical Neurons......Page 303
4.2.2 Cultured Hippocampal Neurons......Page 304
4.4 Basic Fibroblast Growth Factor Receptors......Page 305
References......Page 306
Taurine in Neurotransmission......Page 322
2.1 Occurrence and Distribution......Page 323
2.2 Biosynthesis and Catabolism......Page 324
3.1 Effects on Membrane Ion Conductances......Page 325
3.2 Putative Taurine Receptors......Page 326
4 Taurine Release......Page 327
5.1 Interactions with GABAergic Systems......Page 328
5.2 Interactions with Glycinergic Systems......Page 329
5.3 Interactions with Other Transmitter Systems......Page 330
Acknowledgments......Page 331
References......Page 332
The Endocannabinoid System......Page 340
1 Introduction......Page 342
2.1 Cannabinoid Receptors......Page 343
2.1.1 Glycosylation Sites of Cannabinoid Receptors......Page 345
2.1.3 Cannabinoid Receptor Knockout Mice......Page 346
2.1.4 Polymorphic Structure of Cannabinoid Receptor Genes......Page 348
2.1.6 Localization of Cannabinoid Receptors......Page 349
2.1.7 Signal Transduction Mechanism of Cannabinoid Receptors......Page 350
2.2 Endocannabinoids......Page 352
2.2.1 Anandamide......Page 353
2.2.1.2 Biosynthesis and Metabolism of N-Arachidonylethanolamine......Page 354
2.2.2 2-Arachidonylglycerol......Page 355
2.2.2.1 Biosynthesis and Metabolism of 2-Arachidonylglycerol......Page 356
2.3 Fatty Acid Amide Hydrolase......Page 358
2.3.1 Localization and Distribution of Fatty Acid Amide Hydrolase in the Brain......Page 359
2.4 Endocannabinoids Uptake......Page 360
2.5.1 Regulation of gamma-Aminobutyric Acid Transmission......Page 361
2.5.2 Regulation of Glutamate Transmission......Page 362
2.5.4 Release of Endocannabinoids by Activation of Other Neurotransmitter Receptors......Page 363
2.5.6 Role of Endocannabinoid System in Disease......Page 364
3 Therapeutic Opportunity......Page 367
Acknowledgment......Page 368
References......Page 369
E Prostanoid Receptors in Brain Physiology and Disease......Page 382
2.2 Prostaglandin Pathway......Page 383
2.4 Expression of EP Receptors......Page 384
3.1 Periphery......Page 385
3.2 Central Nervous System......Page 387
3.2.1 Excitotoxicity......Page 388
3.2.3 Innate Immune Response......Page 389
3.2.4 Microglia Phagocytosis of Neurotoxic Peptides......Page 390
4.2.1 Ischemia......Page 391
4.2.3 Parkinson's Disease......Page 392
References......Page 393
Nitric Oxide and other Diffusible Messengers......Page 399
1.1.1 Synthesis of NO......Page 400
1.1.3 Subcellular Localization of NOS......Page 402
1.2 Effector Mechanisms of NO......Page 403
1.3.2 NO and LTP......Page 404
1.3.3 NO as a Nonsynaptic Link between Glutamatergic and Monoaminergic Neurons......Page 405
1.4 NO and Neurotoxicity......Page 406
1.5 NO in the Peripheral Nervous System......Page 407
References......Page 408
Molecular Organization and Regulation of Glutamate Receptors in Developing and Adult Mammalian Central Nervous Systems......Page 410
1 Historical Overview......Page 411
2.1 Ionotropic Glutamate Receptors......Page 412
2.2 Metabotropic Glutamate Receptors......Page 415
3.1 Developmental Changes in AMPA Receptors......Page 416
3.3 Developmental Changes in Kainate Receptors......Page 417
4.1 Synaptic Distribution of Glutamate Receptors......Page 418
4.2 Extrasynaptic Glutamate Receptors......Page 421
5.1.1 Phosphorylation of AMPA Receptors......Page 422
5.1.4 Phosphorylation of mGluRs......Page 424
5.2.1 Recruitment of AMPA Receptors at Synapses......Page 425
5.2.2 Kainate Receptor Trafficking......Page 427
5.2.3 NMDA Receptor Trafficking......Page 428
References......Page 429
Sympathetic and Peptidergic Innervation: Major Role at the Neural-Immune Interface......Page 437
1 The Neural-Immune Interface......Page 438
2 Lymphocyte Traffic and Proliferation......Page 439
4.1 NE and Epinephrine......Page 440
4.3 ATP and NPY......Page 441
5.1 CRH/SP-Mast Cell-Histamine Axis......Page 442
7 Conclusion and Clinical Implications......Page 444
References......Page 446
Index......Page 450