978-3-527-31307-5

1 Introduction 3 1.1 Neuroactive Substances 3 1.1.1 Neurotransmitters 4 1.1.2 Neuromodulators 5 1.2 Receptors and Transporters 8 1.2.1 Ionotropic Receptors 9 1.2.2 Metabotropic Receptors 10 1.2.3 Receptor Regulation 13 1.2.4 Transporters 14 1.3 Distribution and Localization of Neurotransmitters and Neuromodulators 15 1.4 The Blood–Brain Barrier 16 1.5 Volume Transmission and Wiring Transmission 18 2 Methods 21 2.1 Bio- and Radioisotope Assays 22 2.2 Microdialysis and 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 Performance Liquid Chromatography 27 2.3.3 Proteomics: Multidimensional Protein Identification Technology 28 2.4 Autoradiography 30 2.5 Immunohistochemical Methods 31 2.6 In situ Hybridization 33 2.7 Staining and Neuroanatomical Tract Tracing 34 2.8 Electrophysiology 36 2.8.1 In vivo Recording 36 V Contents 2.8.2 In vitro Recording 37 2.9 Behavioral Testing 41 2.9.1 Classic Conditioning 41 2.9.2 Operant Conditioning 42 2.9.3 Further Behavioral Tests 42 3 Neurotransmitters 46 3.1 Acetylcholine 46 3.1.1 General Aspects and History 46 3.1.2 Localization Within the Central Nervous System 47 3.1.3 Biosynthesis and Degradation 48 3.1.4 Receptors and Signal Transduction 49 3.1.5 Biological Effects 55 3.1.6 Neurological Disorders and Neurogenerative Diseases 57 3.2 Dopamine 59 3.2.1 General Aspects and History 59 3.2.2 Differentiation and Localization of the Dopaminergic System 60 3.2.3 Biosynthesis and Degradation 62 3.2.4 Release, Re-uptake and Degradation 64 3.2.5 Receptors and Signal Transduction 65 3.2.6 Biological Effects 69 3.2.7 Neurological Disorders and Neurodegenerative Diseases 70 3.3 -Amino Butyric Acid 75 3.3.1 General Aspects and History 75 3.3.2 Localization Within the Central Nervous System 75 3.3.3 Biosynthesis and Degradation 76 3.3.4 GABA Transporters 77 3.3.5 Receptors and Signal Transduction 78 3.3.6 Biological Effects 84 3.3.7 Neurological Disorders and Neurogenerative Diseases 85 3.4 Glutamate and Aspartate 90 3.4.1 General Aspects and History 90 3.4.2 Localization Within the Central Nervous System 91 3.4.3 Biosynthesis and Degradation 92 3.4.4 Transporters 92 3.4.5 Receptors and Signal Transduction 93 3.4.6 Biological Effects 103 3.4.7 Neurological Disorders and Neurodegenerative Diseases 106 3.5 Glycine 108 3.5.1 General Aspects and History 108 3.5.2 Localization Within the Central Nervous System 109 3.5.3 Biosynthesis and Degradation 109 3.5.4 Receptors and Signal Transduction 110 3.5.5 Biological Effects 113 3.5.6 Neurological Disorders and Neurodegenerative Diseases 113 VI Contents 3.6 Histamine 114 3.6.1 General Aspects and History 114 3.6.2 Localization Within the Central Nervous System 115 3.6.3 Biosynthesis and Degradation 116 3.6.4 Receptors and Signal Transduction 117 3.6.5 Biological Effects 119 3.6.6 Neurological Disorders and Neurodegenerative Diseases 121 3.7 Norepinephrine 123 3.7.1 General Aspects and History 123 3.7.2 Localization Within the Central Nervous System 123 3.7.3 Biosynthesis and Degradation 125 3.7.4 Receptors and Signal Transduction 127 3.7.5 Biological Effects 129 3.7.6 Neurological Disorders and Neurodegenerative Diseases 130 3.8 Serotonin (5-Hydroxytryptamine) 132 3.8.1 General Aspects and History 132 3.8.2 Localization Within the Central Nervous System 133 3.8.3 Biosynthesis and Degradation 133 3.8.4 Receptors and Signal Transduction 135 3.8.5 Biological Effects 139 3.8.6 Neurological Disorders and Neurodegenerative Diseases 139 4 Neuromodulators 144 4.1 Adrenocorticotropic Hormone 144 4.1.1 General Aspects and History 144 4.1.2 Localization Within the Central Nervous System 145 4.1.3 Biosynthesis and Degradation 145 4.1.4 Receptors and Signal Transduction 145 4.1.5 Biological Effects 146 4.1.6 Neurological Disorders and Neurodegenerative Diseases 147 4.2 Anandamide (Endocannabinoids) 149 4.2.1 General Aspects and History 149 4.2.2 Localization Within the Central Nervous System 150 4.2.3 Biosynthesis and Degradation 150 4.2.4 Receptors and Signal Transduction 152 4.2.5 Biological Effects 155 4.2.6 Neurological Disorders and Neurodegenerative Diseases 156 4.3 Angiotensin 158 4.3.1 General Aspects and History 158 4.3.2 Localization Within the Central Nervous System 159 4.3.3 Biosynthesis and Degradation 159 4.3.4 Receptors and Signal Transduction 162 4.3.5 Biological Effects 165 4.3.6 Neurological Disorders and Neurodegenerative Diseases 166 4.4 Atrial Natriuretic Factor 169 Contents VII 4.4.1 General Aspects and History 169 4.4.2 Localization Within the Central Nervous System 169 4.4.3 Biosynthesis and Degradation 170 4.4.4 Receptors and Signal Transduction 171 4.4.5 Biological Effects 172 4.4.6 Neurological Disorders and Neurodegenerative Diseases 173 4.5 Bombesin and Related Neuropeptides 175 4.5.1 General Aspects and History 175 4.5.2 Localization Within the Central Nervous System 175 4.5.3 Biosynthesis and Degradation 176 4.5.4 Receptors and Signal Transduction 176 4.5.5 Biological Effects 177 4.6 Calcitonin and Calcitonin Gene-related Protein 178 4.6.1 General Aspects and History 178 4.6.2 Localization Within the Central Nervous System 179 4.6.3 Biosynthesis and Degradation 180 4.6.4 Receptors and Signal Transduction 180 4.6.5 Biological Effects 182 4.6.6 Neurological Disorders and Neurodegenerative Diseases 183 4.7 Cholecystokinin 184 4.7.1 General Aspects and History 184 4.7.2 Localization Within the Central Nervous System 185 4.7.3 Biosynthesis and Degradation 186 4.7.4 Receptors and Signal Transduction 187 4.7.5 Biological Effects 188 4.7.6 Neurological Disorders and Neurodegenerative Diseases 190 4.8 Corticotropin-releasing Factor 192 4.8.1 General Aspects and History 192 4.8.2 Localization Within the Central Nervous System 192 4.8.3 Biosynthesis and Degradation 194 4.8.4 Receptors and Signal Transduction 195 4.8.5 Biological Effects 196 4.8.6 Neurological Disorders and Neurodegenerative Diseases 196 4.9 Dynorphin 199 4.9.1 General Aspects and History 199 4.9.2 Localization Within the Central Nervous System 200 4.9.3 Biosynthesis and Degradation 201 4.9.4 Receptors and Signal Transduction 202 4.9.5 Biological Effects 203 4.9.6 Neurological Disorders and Neurodegenerative Diseases 203 4.10 Eicosanoids and Arachidonic Acid 205 4.10.1 General and History Aspects 205 4.10.2 Biosynthesis and Degradation 206 4.10.3 Receptors and Signal Transduction 207 4.10.4 Biological Effects 208 VIII Contents 4.10.5 Neurological Disorders and Neurodegenerative Diseases 208 4.11 Endorphin 211 4.11.1 General Aspects and History 211 4.11.2 Localization Within the Central Nervous System 211 4.11.3 Biosynthesis and Degradation 211 4.11.4 Biological Effects 214 4.11.5 Neurological Disorders and Neurodegenerative Diseases 215 4.12 Enkephalin 216 4.12.1 General Aspects and History 216 4.12.2 Localization Within the Central Nervous System 217 4.12.3 Biosynthesis and Degradation 218 4.12.4 Receptors and Signal Transduction 219 4.12.5 Biological Effects 219 4.12.6 Neurological Disorders and Neurodegenerative Diseases 220 4.13 Fibroblast Growth Factors 221 4.13.1 General Aspects and History 221 4.13.2 Localization Within the Central Nervous System 221 4.13.3 Biosynthesis and Degradation 223 4.13.4 Receptors and Signal Transduction 224 4.13.5 Biological Effects 225 4.13.6 Neurological Disorders and Neurodegenerative Diseases 227 4.14 Galanin 229 4.14.1 General Aspects and History 229 4.14.2 Localization Within the Central Nervous System 229 4.14.3 Biosynthesis and Degradation 229 4.14.4 Receptors and Signal Transduction 231 4.14.5 Biological Effects 233 4.14.6 Neurological Disorders and Neurodegenerative Diseases 234 4.15 Ghrelin 235 4.15.1 General Aspects and History 235 4.15.2 Localization Within the Central Nervous System 236 4.15.3 Biosynthesis and Degradation 236 4.15.4 Receptors and Signal Transduction 237 4.15.5 Biological Effects 238 4.15.6 Neurological Disorders and Neurodegenerative Diseases 239 4.16 Gonadotropin-releasing Hormone 240 4.16.1 General Aspects and History 240 4.16.2 Localization Within the Central Nervous System 240 4.16.3 Biosynthesis and Degradation 241 4.16.4 Receptors and Signal Transduction 242 4.16.5 Biological Effects 242 4.16.6 Neurological Disorders and Neurodegenerative Diseases 243 4.17 Growth Hormone-releasing Hormone 244 4.17.1 General Aspects and History 244 4.17.2 Localization Within the Central Nervous System 244 Contents IX 4.17.3 Biosynthesis and Degradation 245 4.17.4 Receptors and Signal Transduction 246 4.17.5 Biological Effects 246 4.17.6 Neurological Disorders and Neurodegenerative Diseases 247 4.18 Hypocretin (Orexin) 248 4.18.1 General Aspects and History 248 4.18.2 Localization Within the Central Nervous System 249 4.18.3 Biosynthesis and Degradation 250 4.18.4 Receptors and Signal Transduction 251 4.18.5 Biological Effects 251 4.18.6 Neurological Disorders and Neurodegenerative Diseases 252 4.19 Interleukin 254 4.19.1 General Aspects 254 4.19.2 Localization Within the Central Nervous System 255 4.19.3 Biosynthesis and Degradation 255 4.19.4 Receptors and Signal Transduction 256 4.19.5 Biological Effects 258 4.19.6 Neurological Disorders and Neurodegenerative Diseases 259 4.20 Melanin-concentrating Hormone 261 4.20.1 General Aspects and History 261 4.20.2 Localization Within the Central Nervous System 262 4.20.3 Biosynthesis and Degradation 262 4.20.4 Receptors and Signal Transduction 263 4.20.5 Biological Effects 263 4.20.6 Neurological Disorders and Neurodegenerative Diseases 265 4.21 Melanocyte-stimulating Hormone 266 4.21.1 General Aspects 266 4.21.2 Localization Within the Central Nervous System 267 4.21.3 Biosynthesis and Degradation 267 4.21.4 Receptors and Signal Transduction 267 4.21.5 Biological Effects 269 4.21.6 Neurological Disorders and Neurodegenerative Diseases 270 4.22 Neuropeptide Y 272 4.22.1 General Aspects and History 272 4.22.2 Localization Within the Central Nervous System 273 4.22.3 Biosynthesis and Degradation 274 4.22.4 Receptors and Signal Transduction 275 4.22.5 Biological Effects 276 4.22.6 Neurological Disorders and Neurodegenerative Diseases 277 4.23 Neurotensin 279 4.23.1 General Aspects and History 279 4.23.2 Localization Within the Central Nervous System 280 4.23.3 Biosynthesis and Degradation 281 4.23.4 Receptors and Signal Transduction 282 4.23.5 Biological Effects 283 X Contents 4.23.6 Neurological Disorders and Neurodegenerative Diseases 284 4.24 Neurotrophins 286 4.24.1 General Aspects and History 286 4.24.2 Localization Within the Central Nervous System 287 4.24.3 Biosynthesis and Degradation 288 4.24.4 Receptors and Signal Transduction 289 4.24.5 Biological Effects 292 4.24.6 Neurological Disorders and Neurodegenerative Diseases 293 4.25 Nitric Oxide and Carbon Monoxide 295 4.25.1 General Aspects and History 295 4.25.2 Localization Within the Central Nervous System 297 4.25.3 Biosynthesis and Degradation 297 4.25.4 Receptors and Signal Transduction 299 4.25.5 Biological Functions 301 4.25.6 Neurological Disorders and Neurodegenerative Diseases 303 4.26 Nociceptin (Orphanin FQ) 305 4.26.1 General Aspects and History 305 4.26.2 Localization Within the Central Nervous System 306 4.26.3 Biosynthesis and Degradation 306 4.26.4 Receptors and Signal Transduction 307 4.26.5 Biological Effects 308 4.26.6 Neurological Disorders and Neurodegenerative Diseases 309 4.27 Pituitary Adenylate Cyclase-activating Polypeptide 311 4.27.1 General Aspects and History 311 4.27.2 Localization Within the Central Nervous System 312 4.27.3 Biosynthesis and Degradation 312 4.27.4 Receptors and Signal Transduction 312 4.27.5 Biological Effects 313 4.27.6 Neurological Disorders and Neurodegenerative Diseases 314 4.28 Proopiomelanocortin 315 4.28.1 General Aspects and History 315 4.28.2 Localization Within the Central Nervous System 316 4.28.3 Biosynthesis and Degradation 316 4.28.4 Receptors and Signal Transduction 318 4.28.5 Biological Effects 318 4.29 Purines 320 4.29.1 General Aspects 320 4.29.2 Biosynthesis and Degradation 321 4.29.3 Receptors and Signal Transduction 321 4.29.4 Biological Effects 324 4.29.5 Neurological Disorders and Neurodegenerative Diseases 325 4.30 Somatostatin 326 4.30.1 General Aspects and History 326 4.30.2 Localization Within the Central Nervous System 327 4.30.3 Biosynthesis and Degradation 328 Contents XI 4.30.4 Receptors and Signal Transduction 329 4.30.5 Biological Effects 331 4.30.6 Neurological Disorders and Neurodegenerative Diseases 332 4.31 Substance P and Tachykinins 334 4.31.1 General Aspects and History 334 4.31.2 Localization Within the Central Nervous System 335 4.31.3 Biosynthesis and Degradation 335 4.31.4 Receptors and Signal Transduction 336 4.31.5 Biological Effects 338 4.31.6 Neurological Disorders and Neurodegenerative Diseases 339 4.32 Thyrotropin-releasing Hormone 341 4.32.1 General Aspects and History 341 4.32.2 Localization Within the Central Nervous System 342 4.32.3 Biosynthesis and Degradation 343 4.32.4 Receptors and Signal Transduction 344 4.32.5 Biological Effects 345 4.32.6 Neurological Disorders and Neurodegenerative Diseases 346 4.33 The Tyr-MIF-1 Family 347 4.34 Vasoactive Intestinal Polypeptide 349 4.34.1 General Aspects and History 349 4.34.2 Localization Within the Central Nervous System 350 4.34.3 Biosynthesis and Degradation 351 4.34.4 Receptors and Signal Transduction 351 4.34.5 Biological Effects 352 4.34.6 Neurological Disorders and Neurodegenerative Diseases 354 4.35 Vasopressin and Oxytocin 355 4.35.1 General Aspects and History 355 4.35.2 Localization Within the Central Nervous System 356 4.35.3 Biosynthesis and Degradation 358 4.35.4 Receptors and Signal Transduction 359 4.35.5 Biological Effects 360 4.35.6 Neurological Disorders and Neurodegenerative Diseases 363 4.36 Deorphanized Neuropeptides 364 4.36.1 Apelin 365 4.36.2 Kisspeptin/Metastin 366 4.36.3 Opiod-modulating Peptides (NPFF and NPAF) 367 A Appendix A1 Amino Acids 369 A2 Nucleotides 372 A3 Abbreviations for Neurotransmitters and Neuromodulators 372 A4 Miscellaneous Abbreviations (Enzymes and Transporters)