Table Of ContentOliver von BohlenundHalbach
andRolf Dermietzel
Neurotransmitters and
Neuromodulators
NeurotransmittersandNeuromodulators.HandbookofReceptorsandBiologicalEffects.2ndEd.
OlivervonBohlenundHalbachandRolfDermietzel
Copyright©2006WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-31307-9
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Oliver von Bohlen und Halbach and Rolf Dermietzel
Neurotransmitters and Neuromodulators
Handbook of Receptors and Biological Effects
2nd completely revised and enlarged edition
TheAuthors (cid:1) AllbookspublishedbyWiley-VCHare
carefullyproduced.Nevertheless,authors,
Dr.OlivervonBohlenundHalbach editors,andpublisherdonotwarrantthe
DepartmentofAnatomyandCellBiology informationcontainedinthesebooks,
UniversityofHeidelberg includingthisbook,tobefreeoferrors.
ImNeuenheimerFeld307 Readersareadvisedtokeepinmindthat
69120Heidelberg statements,data,illustrations,procedural
Germany detailsorotheritemsmayinadvertently
beinaccurate.
Prof.Dr.med.RolfDermietzel
DepartmentofNeuroanatomy
andMolecularBrainResearch LibraryofCongressCardNo.:appliedfor
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tionintheDeutscheNationalbibliografie;detailed
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©2006WILEY-VCHVerlagGmbH&Co.KGaA,
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Allrightsreserved(includingthoseoftranslation
intootherlanguages).Nopartofthisbookmay
bereproducedinanyform–byphotoprinting,
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ISBN-13:978-3-527-31307-5
ISBN-10:3-527-31307-9
V
Contents
Preface for the Second Edition XIII
Preface for the First Edition XV
1 Introduction 3
1.1 NeuroactiveSubstances 3
1.1.1 Neurotransmitters 4
1.1.2 Neuromodulators 5
1.2 Receptorsand Transporters 8
1.2.1 IonotropicReceptors 9
1.2.2 MetabotropicReceptors 10
1.2.3 ReceptorRegulation 13
1.2.4 Transporters 14
1.3 Distributionand LocalizationofNeurotransmitters
and Neuromodulators 15
1.4 The Blood–BrainBarrier 16
1.5 Volume Transmissionand Wiring Transmission 18
2 Methods 21
2.1 Bio-and RadioisotopeAssays 22
2.2 Microdialysisand Electrochemical Detection 24
2.2.1 Microdialysis 24
2.2.2 Electrochemical Detection 24
2.3 Chromatography 26
2.3.1 Affinity Chromatography 26
2.3.2 High PerformanceLiquid Chromatography 27
2.3.3 Proteomics:Multidimensional Protein Identification Technology 28
2.4 Autoradiography 30
2.5 Immunohistochemical Methods 31
2.6 In situHybridization 33
2.7 Staining and Neuroanatomical Tract Tracing 34
2.8 Electrophysiology 36
2.8.1 In vivo Recording 36
NeurotransmittersandNeuromodulators.HandbookofReceptorsandBiologicalEffects.2ndEd.
OlivervonBohlenundHalbachandRolfDermietzel
Copyright©2006WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-31307-9
VI Contents
2.8.2 In vitro Recording 37
2.9 BehavioralTesting 41
2.9.1 ClassicConditioning 41
2.9.2 Operant Conditioning 42
2.9.3 Further BehavioralTests 42
3 Neurotransmitters 46
3.1 Acetylcholine 46
3.1.1 General Aspects and History 46
3.1.2 LocalizationWithin the Central NervousSystem 47
3.1.3 Biosynthesisand Degradation 48
3.1.4 Receptorsand Signal Transduction 49
3.1.5 Biological Effects 55
3.1.6 Neurological Disordersand NeurogenerativeDiseases 57
3.2 Dopamine 59
3.2.1 General Aspects and History 59
3.2.2 Differentiationand Localization ofthe Dopaminergic System 60
3.2.3 Biosynthesisand Degradation 62
3.2.4 Release, Re-uptake and Degradation 64
3.2.5 Receptorsand Signal Transduction 65
3.2.6 Biological Effects 69
3.2.7 Neurological Disordersand NeurodegenerativeDiseases 70
3.3 (cid:1)-Amino Butyric Acid 75
3.3.1 General Aspects and History 75
3.3.2 LocalizationWithin the Central NervousSystem 75
3.3.3 Biosynthesisand Degradation 76
3.3.4 GABATransporters 77
3.3.5 Receptorsand Signal Transduction 78
3.3.6 Biological Effects 84
3.3.7 Neurological Disordersand NeurogenerativeDiseases 85
3.4 Glutamate and Aspartate 90
3.4.1 General Aspects and History 90
3.4.2 LocalizationWithin the Central NervousSystem 91
3.4.3 Biosynthesisand Degradation 92
3.4.4 Transporters 92
3.4.5 Receptorsand Signal Transduction 93
3.4.6 Biological Effects 103
3.4.7 Neurological Disordersand NeurodegenerativeDiseases 106
3.5 Glycine 108
3.5.1 General Aspects and History 108
3.5.2 LocalizationWithin the Central NervousSystem 109
3.5.3 Biosynthesisand Degradation 109
3.5.4 Receptorsand Signal Transduction 110
3.5.5 Biological Effects 113
3.5.6 Neurological Disordersand NeurodegenerativeDiseases 113
Contents VII
3.6 Histamine 114
3.6.1 General Aspects and History 114
3.6.2 LocalizationWithin the Central NervousSystem 115
3.6.3 Biosynthesisand Degradation 116
3.6.4 Receptorsand Signal Transduction 117
3.6.5 Biological Effects 119
3.6.6 Neurological Disordersand NeurodegenerativeDiseases 121
3.7 Norepinephrine 123
3.7.1 General Aspects and History 123
3.7.2 LocalizationWithin the Central NervousSystem 123
3.7.3 Biosynthesisand Degradation 125
3.7.4 Receptorsand Signal Transduction 127
3.7.5 Biological Effects 129
3.7.6 Neurological Disordersand NeurodegenerativeDiseases 130
3.8 Serotonin(5-Hydroxytryptamine) 132
3.8.1 General Aspects and History 132
3.8.2 LocalizationWithin the Central NervousSystem 133
3.8.3 Biosynthesisand Degradation 133
3.8.4 Receptorsand Signal Transduction 135
3.8.5 Biological Effects 139
3.8.6 Neurological Disordersand NeurodegenerativeDiseases 139
4 Neuromodulators 144
4.1 AdrenocorticotropicHormone 144
4.1.1 General Aspects and History 144
4.1.2 LocalizationWithin the Central NervousSystem 145
4.1.3 Biosynthesisand Degradation 145
4.1.4 Receptorsand Signal Transduction 145
4.1.5 Biological Effects 146
4.1.6 Neurological Disordersand NeurodegenerativeDiseases 147
4.2 Anandamide (Endocannabinoids) 149
4.2.1 General Aspects and History 149
4.2.2 LocalizationWithin the Central NervousSystem 150
4.2.3 Biosynthesisand Degradation 150
4.2.4 Receptorsand Signal Transduction 152
4.2.5 Biological Effects 155
4.2.6 Neurological Disordersand NeurodegenerativeDiseases 156
4.3 Angiotensin 158
4.3.1 General Aspects and History 158
4.3.2 LocalizationWithin the Central NervousSystem 159
4.3.3 Biosynthesisand Degradation 159
4.3.4 Receptorsand Signal Transduction 162
4.3.5 Biological Effects 165
4.3.6 Neurological Disordersand NeurodegenerativeDiseases 166
4.4 Atrial Natriuretic Factor 169
VIII Contents
4.4.1 General Aspects and History 169
4.4.2 LocalizationWithin the Central NervousSystem 169
4.4.3 Biosynthesisand Degradation 170
4.4.4 Receptorsand Signal Transduction 171
4.4.5 Biological Effects 172
4.4.6 Neurological Disordersand NeurodegenerativeDiseases 173
4.5 Bombesinand Related Neuropeptides 175
4.5.1 General Aspects and History 175
4.5.2 LocalizationWithin the Central NervousSystem 175
4.5.3 Biosynthesisand Degradation 176
4.5.4 Receptorsand Signal Transduction 176
4.5.5 Biological Effects 177
4.6 Calcitonin and Calcitonin Gene-relatedProtein 178
4.6.1 General Aspects and History 178
4.6.2 LocalizationWithin the Central NervousSystem 179
4.6.3 Biosynthesisand Degradation 180
4.6.4 Receptorsand Signal Transduction 180
4.6.5 Biological Effects 182
4.6.6 Neurological Disordersand NeurodegenerativeDiseases 183
4.7 Cholecystokinin 184
4.7.1 General Aspects and History 184
4.7.2 LocalizationWithin the Central NervousSystem 185
4.7.3 Biosynthesisand Degradation 186
4.7.4 Receptorsand Signal Transduction 187
4.7.5 Biological Effects 188
4.7.6 Neurological Disordersand NeurodegenerativeDiseases 190
4.8 Corticotropin-releasingFactor 192
4.8.1 General Aspects and History 192
4.8.2 LocalizationWithin the Central NervousSystem 192
4.8.3 Biosynthesisand Degradation 194
4.8.4 Receptorsand Signal Transduction 195
4.8.5 Biological Effects 196
4.8.6 Neurological Disordersand NeurodegenerativeDiseases 196
4.9 Dynorphin 199
4.9.1 General Aspects and History 199
4.9.2 LocalizationWithin the Central NervousSystem 200
4.9.3 Biosynthesisand Degradation 201
4.9.4 Receptorsand Signal Transduction 202
4.9.5 Biological Effects 203
4.9.6 Neurological Disordersand NeurodegenerativeDiseases 203
4.10 Eicosanoidsand Arachidonic Acid 205
4.10.1 General and HistoryAspects 205
4.10.2 Biosynthesisand Degradation 206
4.10.3 Receptorsand Signal Transduction 207
4.10.4 Biological Effects 208
Contents IX
4.10.5 Neurological Disordersand NeurodegenerativeDiseases 208
4.11 Endorphin 211
4.11.1 General Aspects and History 211
4.11.2 LocalizationWithin the Central NervousSystem 211
4.11.3 Biosynthesisand Degradation 211
4.11.4 Biological Effects 214
4.11.5 Neurological Disordersand NeurodegenerativeDiseases 215
4.12 Enkephalin 216
4.12.1 General Aspects and History 216
4.12.2 LocalizationWithin the Central NervousSystem 217
4.12.3 Biosynthesisand Degradation 218
4.12.4 Receptorsand Signal Transduction 219
4.12.5 Biological Effects 219
4.12.6 Neurological Disordersand NeurodegenerativeDiseases 220
4.13 FibroblastGrowth Factors 221
4.13.1 General Aspects and History 221
4.13.2 LocalizationWithin the Central NervousSystem 221
4.13.3 Biosynthesisand Degradation 223
4.13.4 Receptorsand Signal Transduction 224
4.13.5 Biological Effects 225
4.13.6 Neurological Disordersand NeurodegenerativeDiseases 227
4.14 Galanin 229
4.14.1 General Aspects and History 229
4.14.2 LocalizationWithin the Central NervousSystem 229
4.14.3 Biosynthesisand Degradation 229
4.14.4 Receptorsand Signal Transduction 231
4.14.5 Biological Effects 233
4.14.6 Neurological Disordersand NeurodegenerativeDiseases 234
4.15 Ghrelin 235
4.15.1 General Aspects and History 235
4.15.2 LocalizationWithin the Central NervousSystem 236
4.15.3 Biosynthesisand Degradation 236
4.15.4 Receptorsand Signal Transduction 237
4.15.5 Biological Effects 238
4.15.6 Neurological Disordersand NeurodegenerativeDiseases 239
4.16 Gonadotropin-releasingHormone 240
4.16.1 General Aspects and History 240
4.16.2 LocalizationWithin the Central NervousSystem 240
4.16.3 Biosynthesisand Degradation 241
4.16.4 Receptorsand Signal Transduction 242
4.16.5 Biological Effects 242
4.16.6 Neurological Disordersand NeurodegenerativeDiseases 243
4.17 Growth Hormone-releasingHormone 244
4.17.1 General Aspects and History 244
4.17.2 LocalizationWithin the Central NervousSystem 244
X Contents
4.17.3 Biosynthesisand Degradation 245
4.17.4 Receptorsand Signal Transduction 246
4.17.5 Biological Effects 246
4.17.6 Neurological Disordersand NeurodegenerativeDiseases 247
4.18 Hypocretin(Orexin) 248
4.18.1 General Aspects and History 248
4.18.2 LocalizationWithin the Central NervousSystem 249
4.18.3 Biosynthesisand Degradation 250
4.18.4 Receptorsand Signal Transduction 251
4.18.5 Biological Effects 251
4.18.6 Neurological Disordersand NeurodegenerativeDiseases 252
4.19 Interleukin 254
4.19.1 General Aspects 254
4.19.2 LocalizationWithin the Central NervousSystem 255
4.19.3 Biosynthesisand Degradation 255
4.19.4 Receptorsand Signal Transduction 256
4.19.5 Biological Effects 258
4.19.6 Neurological Disordersand NeurodegenerativeDiseases 259
4.20 Melanin-concentrating Hormone 261
4.20.1 General Aspects and History 261
4.20.2 LocalizationWithin the Central NervousSystem 262
4.20.3 Biosynthesisand Degradation 262
4.20.4 Receptorsand Signal Transduction 263
4.20.5 Biological Effects 263
4.20.6 Neurological Disordersand NeurodegenerativeDiseases 265
4.21 Melanocyte-stimulating Hormone 266
4.21.1 General Aspects 266
4.21.2 LocalizationWithin the Central NervousSystem 267
4.21.3 Biosynthesisand Degradation 267
4.21.4 Receptorsand Signal Transduction 267
4.21.5 Biological Effects 269
4.21.6 Neurological Disordersand NeurodegenerativeDiseases 270
4.22 Neuropeptide Y 272
4.22.1 General Aspects and History 272
4.22.2 LocalizationWithin the Central NervousSystem 273
4.22.3 Biosynthesisand Degradation 274
4.22.4 Receptorsand Signal Transduction 275
4.22.5 Biological Effects 276
4.22.6 Neurological Disordersand NeurodegenerativeDiseases 277
4.23 Neurotensin 279
4.23.1 General Aspects and History 279
4.23.2 LocalizationWithin the Central NervousSystem 280
4.23.3 Biosynthesisand Degradation 281
4.23.4 Receptorsand Signal Transduction 282
4.23.5 Biological Effects 283
