Advances in Endogenous and Exogenous Opioids (eBook)

Front Cover 1
Advances in Endogenous and Exogenous Opioids 4
Copyright Page 5
Preface 8
Acknowledgements 10
List of Participants 12
Table of Contents 16
Part I: MULTIPLE OPIOID RECEPTORS 28
Chapter 1. THE INTERACTION OF OPIOID PEPTIDES AND ALKALOID OPIATES WITH µ-, d- AND .- BINDING SITES 29
INTRODUCTION 29
METHODS 29
RESULTS 30
ACKNOWLEDGEMENTS 31
REFERENCES 31
Chapter 2. CHARACTERIZATION OF NOVEL OPIATE BINDING SITES SELECTIVE FOR BENZOMORPHAN DRUGS 32
SUMMARY 32
INTRODUCTION 32
METHODS 33
RESULTS AND DISCUSSION 33
REFERENCES 35
Chapter 3. BIOCHEMICAL EVIDENCE FOR KAPPA AND SIGMA OPIATE RECEPTORS 36
BIOCHEMICAL EVIDENCE FOR KAPPA AND SIGMA OPIATE RECEPTORS 36
SUMMARY 36
INTRODUCTION 36
METHODS 36
RESULTS 37
DISCUSSION 38
REFERENCES 38
Chapter 4. CHARACTERIZATION OF DYNORPHIN RECEPTOR SPECIFICITY IN THE GUINEA PIG ILEUM 39
SUMMARY 39
REFERENCES 41
Chapter 5. OPIATE RECEPTORS IN THE GUINEA-PIG ILEAL MUCOSA 42
SUMMARY 42
INTRODUCTION 42
METHODS 42
REFERENCES 44
Chapter 6. OPIATE BINDING SITES IN THE LUMBO-SACRAL SPINAL CORD FROM VARIOUS SPECIES 45
SUMMARY 45
INTRODUCTION 45
METHODS 45
RESULTS 46
DISCUSSION 47
REFERENCES 47
Chapter 7. EFFECTS OF OPIOID PEPTIDES AND KAPPA-RECEPTOR AGONISTS ON IN VITRO ISOLATEDPREPARATIONS 48
SUMMARY 48
INTRODUCTION 48
METHODS 48
RESULTS 49
DISCUSSION 49
REFERENCES 50
Chapter 8. MULTIPLE BENZOMORPHAN BINDING SITES IN A CLONAL CELL LINE 51
SUMMARY 51
METHODS 51
DISCUSSION 53
REFERENCES 53
Chapter 9. MORPHINE AND OXYMORPHONE ACT AS PARTIAL AGONISTS ON THE FIELD STIMULATED RAT VAS DEFERENS 54
SUMMARY 54
INTRODUCTION 54
METHODS 55
RESULTS 55
DISCUSSION 55
REFERENCES 56
Chapter 10. SPECIFIC OPIATE BINDING SITES IN HUMAN PLACENTA 57
SUMMARY 57
INTRODUCTION 57
METHODS 57
RESULTS 57
DISCUSSION 59
REFERENCES 59
Chapter 11. MULTIPLE BINDING SITES FOR 3H-ETHYLKETOCYCLAZOCINE ON THE LUMBO-SACRAL PORTIONOF THE GUINEA-PIG SPINAL CORD 60
SUMMARY 60
INTRODUCTION 60
METHODS 60
RESULTS 61
DISCUSSION 62
REFERENCES 62
Chapter 12. DIFFERENTIAL INTERACTIONS OF DYNORPHIN(1-13), ß-ENDORPHIN, AND ENKEPHALIN-RELATED PEPTIDES AT µ AND d SITES IN DIFFERENT BRAIN REGIONS 63
SUMMARY 63
INTRODUCTION 63
METHODS 63
RESULTS 63
DISCUSSION 65
REFERENCES 65
Chapter 13. DIFFERENTIAL EFFECTS OF ISOMERS OF OPIOID ANTAGONISTS UPON µ-, K- and d AGONIST ANALGESIA: COMPARISON WITH OXOTREMORINE. 66
SUMMARY 66
INTRODUCTION 66
METHODS 66
RESULTS 66
DISCUSSION 68
REFERENCES 68
Chapter 14. POTENCIES OF "MU" AND "KAPPA" AGONISTS ON SMOOTH MUSCLE PREPARATIONS RELATIVE TO DISPLACEMENT OF 3H-ETORPHINE IN ISOLATED RAT BRAIN NEURAL MEMBRANES 69
SUMMARY 69
INTRODUCTION 69
METHODS 69
RESULTS AND DISCUSSION 70
ACKNOWLEDGEMENT 71
REFERENCES 71
Chapter 15. COMPARISON OF 3H-ETORPHINE AND 3H-DIPRENORPHINE RECEPTOR BINDING IN VIVO AND IN VITRO 72
SUMMARY 72
INTRODUCTION 72
METHODS 72
RESULTS 73
DISCUSSION 74
REFERENCES 74
Chapter 16. TENTATIVE IDENTIFICATION OF HIGH AFFINITY OPIOID BINDING SITES IN THE PEDAL GANGLIA OF THE MARINE MUSSEL Mytilus edulis 75
SUMMARY 75
INTRODUCTION 75
METHODS 75
RESULTS 75
DISCUSSION 77
REFERENCES 77
Chapter 17. OPIOID RECEPTORS ON RAT MAST CELLS 78
SUMMARY 78
INTRODUCTION 78
METHODS 78
RESULTS AND DISCUSSION 79
REFERENCES 80
Chapter 18. MECHANISMS OF SUPERSENSITIVITY IN THE ENKEPHALINERGIC SYSTEM 81
SUMMARY 81
INTRODUCTION 81
METHODS 81
RESULTS 82
DISCUSSION 83
REFERENCES 83
Chapter 19. POSTNATAL DEVELOPMENT OF OPIOID MECHANISMS IN RAT VAS DEFERENS 84
SUMMARY 84
INTRODUCTION 84
METHODS 84
RESULTS 85
DISCUSSION 86
REFERENCES 86
Chapter 20. DEVELOPMENTAL DIFFERENCES OF METHIONINE ENKEPHALIN AND NALOXONE BINDING SITES INREGIONS OF RAT BRAIN 87
SUMMARY 87
INTRODUCTION 87
METHODS 87
RESULTS 87
DISCUSSION 88
REFERENCES 89
Chapter 21. µ, d AND OPIATE RECEPTORS: INTERCONVERTIBLE FORMS OF THE SAME RECEPTOR 90
SUMMARY 90
INTRODUCTION 90
METHODS 90
RESULTS AND DISCUSSION 91
REFERENCES 92
PART II: PURIFICATION AND NATURE OF OPIOID RECEPTORS AND SEQUELLAE OF RECEPTOR BINDING 94
Chapter 22. CHARACTERIZATION OF SOLUBILIZED ACTIVE OPIATE RECEPTORS FROM TOAD BRAIN 95
SUMMARY 95
INTRODUCTION 95
METHODS 95
RESULTS 96
DISCUSSION 97
REFERENCES 97
Chapter 23. MULTIPLE ETORPHINE BINDING PROTEINS FROM BRAIN 98
SUMMARY 98
INTRODUCTION 98
METHODS 98
RESULTS 99
DISCUSSION 100
REFERENCES 100
Chapter 24. DIFFERENCES BETWEEN THE OPATE RECEPTOR AND THE ENKEPHALIN RECEPTOR IN RAT BRAIN 101
SUMMARY 101
INTRODUCTION 101
MATERIALS AND METHODS 101
RESULTS AND DISCUSSION 102
REFERENCES 103
Chapter 25. PROPERTIES OF THE SOLUBILIZED OPIATE RECEPTOR FROM HUMAN PLACENTA 104
SUMMARY 104
INTRODUCTION 104
EXPERIMENTAL PROCEDURES 104
METHODS 105
RESULTS AND DISCUSSION 105
REFERENCES 106
Chapter 26. ISOLATION OF AN OPIATE RECEPTOR AND THE EFFECT OF MEMBRANE LIPIDS ON ISOLATEDRECEPTOR BINDING 107
SUMMARY 107
INTRODUCTION 107
METHODS 107
RESULTS 107
DISCUSSION 108
ACKNOWLEDGEMENTS 109
REFERENCES 109
Chapter 27. PHOSPHATIDYL INOSITOL AS A BINDING COMPONENT OF OPIOID RECEPTOR 110
SUMMARY 110
INTRODUCTION 110
MATERIALS AND METHOD 110
RESULTS AND DISCUSSION 111
REFERENCES 112
Chapter 28. SELECTIVITY OF OPIATE AMD OPIOID PEPTIDE INTERACTION WITH CEREBROSIDE SULFATE 113
SUMMARY 113
INTRODUCTION 113
METHODS 113
RESULTS 113
DISCUSSION 115
REFERENCES 115
Chapter 29. IRREVERSIBLE PHOTOACTIVATION OF THE OPIATE RECEPTORS IN THE GUINEA-PIG ILEUM BY SOME ENKEPHAL IN DERIVATIVES 116
SUMMARY 116
INTRODUCTION 116
MATERIALS and METHODS 116
RESULTS 117
DISCUSSION 118
REFERENCES 118
Chapter 30. EFFECTS OF SULFHYDRYL-PROTECTING REAGENTS ON OPIOID RECEPTOR BINDING SITE(S) 119
SUMMARY 119
INTRODUCTION 119
MATERIALS AND METHOD 119
RESULTS AND DISCUSSION 120
REFERENCES 121
Chapter 31. STIMULATION AND DESENSITIZATION OF cGMP FORMATION BY OPIOID AGONISTS IN CLONEDNEUROBLASTOMA CELLS 122
SUMMARY 122
INTRODUCTION 122
METHODS 123
RESULTS AND DISCUSSION 123
REFERENCES 124
Chapter 32. ASCORBATE SUPPRESSES OPIATE INDUCED COMPENSATORY INCREASE IN CYCLIC AMP LEVELS IN NEUROBLASTOMA X GLIOMA HYBRID CELLS 125
SUMMARY 125
INTRODUCTION 125
METHODS 125
RESULTS 126
DISCUSSION 127
ACKNOWLEDGEMENT 127
REFERENCES 128
Chapter 33. A CASE AGAINST RECEPTOR OCCUPANCY AS THE SOLE DETERMINANT IN THE OPIATE REGULATION OF ADENYLATE CYCLASE ACTIVITY IN NEUROBLASTOMA CELLS 129
SUMMARY 129
INTRODUCTION 129
METHODS 130
RESULTS 130
DISCUSSION 131
REFERENCES 132
Chapter 34. INCREASE IN PLASMA CYCLIC NUCLEOTIDE LEVELS INDUCED BY MORPHINE IN MALE MICE 133
SUMMARY 133
INTRODUCTION 133
METHODS 134
RESULTS 134
DISCUSSION 135
REFERENCES 135
PART III: BIOSYNTHESIS OF OPIOID PEPTIDES 136
Chapter 35. STRUCTURAL ORGANIZATION OF THE C0RTICOTROPIN-ß-LIPOTROPIN PRECURSOR GENE 137
SUMMARY 137
INTRODUCTION 137
METHODS 137
RESULTS 138
DISCUSSION 139
REFERENCES 139
Chapter 36. BIOSYNTHESIS AND MATURATION OF PRO-OPIOMEL ANOCORTIN 140
SUMMARY 140
INTRODUCTION 140
RESULTS 140
REFERENCES 142
Chapter 37. MULTIPLE FORMS OF BETA-ENDORPHIN (ßE) IN PITUITARY AND BRAIN: EFFECT OF STRESS 143
INTRODUCTION 143
METHODS 143
CONCLUSION AND DISCUSSION 145
REFERENCES 145
Chapter 38. CALCITONIN-LIKE PEPTIDE IN PRO-OPIOCORTIN: FUNCTIONAL ASPECTS 146
SUMMARY 146
THE LIGAND 146
EXCESS IN OBESE RATS 146
THE RECEPTOR 147
THE PHYSIOLOGY 147
REFERENCES 147
Chapter 39.EFFECT OF MORPHINE OR ALCOHOL TREATMENT ON THE BIOSYNTHESIS OF ß-END0RPHIN BY THE NEUROINTERMEDIATE LOBE 149
SUMMARY 149
INTRODUCTION 149
METHODS 149
RESULTS 150
DISCUSSION 150
REFERENCES 151
Chapter 40. MEMBRANES OF BOVINE CHROMAFFIN GRANULES CONTAIN ENKEPHALIN PRECURSORS LARGER THAN 100,000 DALTONS. 152
DISTRIBUTION OF ENKEPHALIN PRECURSORS IN THE BOVINE ADRENAL MEDULLA 152
CHARACTERIZATION OF THE OVER 100,000 DALTON MATERIAL 154
ACKNOWLEDGEMENTS 154
REFERENCES 154
Chapter 41. PROENKEPHALIN AND INTERMEDIATES IN THE BIOSYNTHESIS OF ENKEPHALINS: Sadao 155
REFERENCES 157
Chapter 42. "BIG" ENKEPHALINS FROM BOVINE ADRENOMEDULLARY GLAND 158
SUMMARY 158
INTRODUCTION 158
METHODS 158
RESULTS AND DISCUSSION 159
REFERENCES 160
Chapter 43. CONVERSION OF MET-ENKEPHALIN-Arg6-Phe7 TO MET-ENKEPHALIN BY DIPEPTIDYL CARBOXYPEPTIDASE 161
SUMMARY 161
INTRODUCTION 161
METHODS 161
RESULTS 162
DISCUSSION 163
REFERENCES 163
PART IV: ENDOGENOUS NOVEL OPIOID PEPTIDES 164
Chapter 44. SEARCH FOR MORPHINE-ANTAGONISTIC AGENTS IN HUMAN CSF AND BRAIN 165
SUMMARY 165
INTRODUCTION 165
METHODS 165
RESULT AND DISCUSSION 166
ACKNOWLEDGEMENTS 167
REFERENCES 167
Chapter 45. H-ENDORPHIN, A NOVEL ENDOGENOUS OPIOID WITH UNCONVENTIONAL NALOXONE INTERACTIONS. 169
INTRODUCTION 169
RESULTS 169
CONCLUSIONS 171
REFERENCES 171
Chapter 46. ISOLATION AND IDENTIFICATION OF TWO NEW PEPTIDES RELATED TO ß-ENDORPHIN 172
SUMMARY 172
INTRODUCTION 172
METHODS 172
RESULTS AND DISCUSSION 173
REFERENCES 175
Chapter 47. ISOLATION OF DYNORPHIN-LIKE PEPTIDE FROM GUT EXTRACT 176
SUMMARY 176
INTRODUCTION 176
MATERIALS AND METHODS 176
RESULTS AND DISCUSSION 177
REFERENCES 178
Chapter 48. SUBSTANTIAL AMOUNTS OF IMMUNOREACTIVE BAM-12P AND BAM-22P ARE PRESENT IN BOVINE ADRENAL MEDULLA BUT NOT IN THE BRAIN 179
SUMMARY 179
INTRODUCTION 179
METHOD 179
RESULTS 180
REFERENCES 181
Chapter 49. DETECTION OF a-N-ACETYL ß-ENDORPHINS IN PITUITARY BY SPECIFIC ANTIBODIES 182
SUMMARY 182
INTRODUCTION 182
METHODS 182
RESULTS AND DISCUSSION 183
REFERENCES 184
PART V: LOCALIZATION RELEASE AND DEGRADATION OF OPIOID PEPTIDES 186
Chapter 50. REGIONAL DISTRIBUTION OF IMMUNOREACTIVE "BIG" LEU-ENKEPHALINS INBRAIN AND PITUITARY 187
SUMMARY 187
INTRODUCTION 187
METHODS 187
RESULTS AND DISCUSSION 188
REFERENCES 189
Chapter 51. ANATOMICAL AND BIOCHEMICAL STUDIES OF DYNORPHIN 190
SUMMARY 190
INTRODUCTION 190
METHODS AND RESULTS 190
REFERENCES 192
ACKNOWLEDGEMENT 192
Chapter 52. ß-ENDORPHIN IN THE BRAIN AND PITUITARY EVIDENCE FOR TWO SPECIFIC PROCESSING PATTERNS
SUMMARY 193
INTRODUCTION 193
METHODS 194
RESULTS AND DISCUSSION 194
REFERENCES 196
Chapter 53. MEASUREMENT OF MET-ENKEPHALIN(ARG6 ,PHE7 ) IN RAT BRAIN BY SPECIFIC RADIOIMMUNOASSAY DIRECTED AT METHIONINE SULPHOXIDE ENKEPHALIN(ARG6 , PHE7 ) 197
SUMMARY 197
INTRODUCTION 197
METHODS 197
RESULTS 198
DISCUSSION 199
REFERENCES: 199
Chapter 54. OPIOID PEPTIDE IN THE DOG CANINE PULP? 200
SUMMARY 200
INTRODUCTION 200
METHOD 200
RESULTS 201
DISCUSSION 202
ACKNOWLEDGEMENTS 202
REFERENCES 202
Chapter 55. SUBCELLULAR LOCALIZATION OF ANALGESIC DIPEPTIDE, KYOTORPHIN (TYR-ARG) IN THERAT BRAIN 203
SUMMARY 203
INTRODUCTION 203
METHODS 203
RESULTS 204
DISCUSSION 204
REFERENCES 205
Chapter 56. RELEASE OF ENDOGENOUS OPIOIDS FROM SPINAL CORD IN VIVO FOLLOWING SCIATIC NERVE STIMULATION. 206
SUMMARY 206
INTRODUCTION 206
METHODS 206
RESULTS 207
DISCUSSION 208
ACKNOWLEDGEMENTS 208
REFERENCES 208
Chapter 57. NOXIOUS STIMULUS-INDUCED RELEASE OF MET-ENKEPHALIN FROM THE NUCLEUS RETICULARIS GIGANTOCELLULARIS OF THE RAT 209
SUMMARY 209
INTRODUCTION 209
METHODS 209
RESULTS 210
DISCUSSION 211
REFERENCES 211
Chapter 58. INTESTINAL OPIOIDS MAY MODULATE THE ACTION OF ACETYLCHOLINE ON PERISTALSIS IN VITRO. RELEASE STUDIES POINT TO A POSSIBLE ROLE FOR DYNORPHIN IN THE CONTROLOF PERISTALSIS. 212
SUMMARY 212
INTRODUCTION 212
METHODS 212
RESULTS 213
DISCUSSION 214
REFERENCES 214
Chapter 59. INHIBITION OF THEIR BREAKDOWN AND RELEASE OF ENDOGENOUS OPIOID PEPTIDES FROM THE MYENTERIC PLEXUS-LONGITUDINAL MUSCLE OF THE GUINEA-PIG ILEUM 215
SUMMARY 215
INTRODUCTION 215
METHODS 215
RESULTS 216
DISCUSSION 217
ACKNOWLEDGEMENTS 217
REFERENCES 217
Chapter 60. PROPERTIES OF ENKEPHALINASE FROM MOUSE AND HUMAN BRAIN 218
INTRODUCTION 218
DISCUSSION 220
REFERENCES 221
Chapter 61. DISCRETE REGIONAL DISTRIBUTION FOR ENKEPHALINASE AND AMINOPEPTIDASE IN MICRODISSECTED RAT BRAIN 222
SUMMARY 222
INTRODUCTION 222
METHODS 222
RESULTS 222
DISCUSSION 224
REFERENCES 224
PART VI: PHYSIOLOGICAL AND PHARMACOLOGICAL ACTIONS OF OPIOIDS 226
Chapter 62. OPIATES CAUSE ACTIVATION OF A CALCIUM-DEPENDENT POTASSIUM CONDUCTANCE 227
REFERENCES 228
Chapter 63. ENKEPHALINERGIC PRESYNAPTIC INHIBITION IN MAMMALIAN SYMPATHETIC GANGLIA 229
SUMMARY 229
INTRODUCTION 229
NALOXONE-REVERSIBLE PRESYNAPTIC INHIBITION OF CHOLINERGIC TRANSMISSION FOLLOWING PREGANGLIONIC NERVE STIMULATION 229
INHIBITORY EFFECT OF ENK ON SP-CONTAINING AFFERENT NERVE TERMINALS IN THE GANGLIA 231
CONCLUSION 231
REFERENCES 231
Chapter 64. ACTIONS OF ENKEPHALIN ON SINGLE NEURONS IN CILIARY GANGLIA 232
SUMMARY 232
INTRODUCTION 232
METHODS 232
RESULTS 233
DISCUSSION 234
REFERENCES 234
Chapter 65. THE DISTRIBUTION OF RECEPTORS FOR ENKEPHALIN AND MORPHINE IN THE DORSAL HORN OF THE CAT 235
SUMMARY 235
INTRODUCTION 235
METHODS 235
RESULTS 236
DISCUSSION 236
REFERENCES 237
Chapter 66. MUTUAL INHIBITION OF SPINAL NOCICEPTIVE PATHWAYS 238
SUMMARY 238
INTRODUCTION 238
METHODS 239
RESULTS AND DISCUSSION 239
ACKNOWLEDGEMENTS 240
REFERENCES 240
Chapter 67. DIFFERENTIAL EFFECTS OF OPIOIDS ON SINGLE NEURONES IN RAT BRAIN 241
METHODS 241
RESULTS 242
DISCUSSION 242
REFERENCES 243
Chapter 68. POSSIBLE EXISTENCE OF ENKEPHALINERGIC NEURONS IN THE STRIATO-PALLIDAL PATHWAY INTHE RAT BRAIN 244
SUMMARY 244
INTRODUCTION 244
METHODS 244
RESULTS AND DISCUSSION 245
REFERENCES 246
Chapter 69. EXCITATORY ACTION OF MICROELECTROPHORETICALLY APPLIED KYOTORPHIN (TYR-ARG) ONUNITARY ACTIVITY IN THE RAT CEREBRAL CORTEX 247
SUMMARY 247
INTRODUCTION 247
METHODS 248
RESULTS 248
DISCUSSION 249
REFERENCES 249
Chapter 70. ENDORPHINS AS MEDIATORS OF ETHANOL ACTIONS: MULTIDISCIPLINARY TESTS 250
SUMMARY 250
INTRODUCTION 250
METHODS 251
RESULTS 251
DISCUSSION 252
REFERENCES 252
Chapter 71. THE MDDULATORY EFFECT OF MORPHINE AND MONOAMINE OXIDASE B (MAO-B) SYSTEM ON ENKEPHALIN-INDUCED SEIZURES 253
SUMMARY 253
INTRODUCTION 253
METHODS 253
RESULTS 254
DISCUSSION 255
REFERENCES 255
Chapter 72. USE OF THE NOVEL OPIATE, ß-FUNALTREXAMINE (ß-FNA) IN THE ELUCIDATION OF RECEPTOR TYPES INVOLVED IN OPIATE-MEDIATED RESPIRATORY DEPRESSION 256
SUMMARY 256
INTRODUCTION 256
METHODS 256
RESULTS 257
DISCUSSION 258
REFERENCES 258
Chapter 73. DIURNAL RHYTHM IN RESPONSE TO NOXIOUS STIMULI - INCREASE OF MET-ENKEPHALIN INGLOBUS PALLIDUS 259
SUMMARY 259
INTRODUCTION 259
METHODS 259
RESULTS 260
DISCUSSION 260
REFERENCES 261
Chapter 74. EFFECTS OF PSYCHOTROPIC DRUGS ON THE LEVELS OF ENKEPHALINS, THEIR RECEPTORS AND ENKEPHALINASE IN RAT BRAIN 262
SUMMARY 262
INTRODUCTION 262
METHODS 262
RESULTS AND DISCUSSION 263
REFERENCES 264
Chapter 75. CHANGES OF BRAIN IMMUNOREACTIVE DYNORPHIN CONTENT FOLLOWING AMYGDALOID-KINDLED AND RECCURENT SEIZURES 265
SUMMARY 265
INTRODUCTION 265
METHODS 265
RESULTS 266
DISCUSSION 267
REFERENCES 267
Chapter 76. EFFECTS OF FEEDING AND DRINKING ON IMMUNOREACTIVE BETA-ENDORPHIN AND ACTH LEVELS IN PLASMA AND HYPOTHALAMUS IN RATS. 268
SUMMARY 268
INTRODUCTION 268
METHODS 268
RESULTS 269
DISCUSSION 270
REFERENCES 270
Chapter 77. PITUITARY ENDORPHIN LEVELS FOLLOWING THE ADMINISTRATION OF BENZAMIDE SUBSTITUTES 271
SUMMARY 271
INTRODUCTION 271
METHODS 271
RESULTS 272
DISCUSSION 272
REFERENCES 273
Chapter 78. OPIOID AND DOPAMINE RECEPTOR INTERACTIONS IN MAMMALIAN BRAIN 274
SUMMARY 274
INTRODUCTION 274
METHODS 274
RESULTS 274
DISCUSSION 276
REFERENCES 276
Chapter 79. THE ROLE OF DOPAMINERGIC SYSTEM ON MORPHINE ANALGESIA IN MICE 277
SUMMARY 277
INTRODUCTION 277
METHODS 277
RESULTS 278
DISCUSSION 278
REFERENCES 279
Chapter 80. MORPHINE PRODUCES DIFFERENT EFFECTS ON SUBTYPES OF MESENCEPHALIC DOPAMINE SYSTEMS 280
SUMMARY 280
INTRODUCTION 280
METHODS 281
RESULTS 281
DISCUSSION 282
REFERENCES 283
Chapter 81. EFFECT OF ADRENERGIC DRUGS ON THE CENTRAL ANTIDIURETIC ACTION OF MORPHINE IN RATS 284
SUMMARY 284
INTRODUCTION 284
EXPERIMENTAL PROCEDURES 284
RESULTS 284
DISCUSSION 285
REFERENCES 286
Chapter 82. EFFECT OF MORPHINE ON ATP-STIMULATED 45Ca++ UPTAKE IN SUBCELLULAR FRACTIONS OF RAT BRAIN. 287
SUMMARY 287
INTRODUCTION 287
METHODS 287
RESULTS 288
DISCUSSION 289
REFERENCES 289
PART VII: ANALGESIA AND ACUPUNCTURE 290
Chapter 83. SPINAL MECHANISMS IN THE EFFECTS OF FENTANYL AND MORPHINE ON THE RAT TAIL FLICKa) 291
SUMMARY 291
INTRODUCTION 291
METHODS 291
RESULTS 291
DISCUSSION 293
REFERENCES 293
Chapter 84. STRONG ANALGESIC ACTIVITY OF LEU-ENKEPHALIN AFTER INHIBITION OF BRAIN AMINOPEPTIDASE: A PHARMACOLOGICAL STUDY. 294
SUMMARY 294
INTRODUCTION 294
METHODS 295
RESULTS 295
DISCUSSION 296
ACKNOWLEDGEMENTS 296
REFERENCES 296
Chapter 85. OPIOID AND NONOPIOID MECHANISMS OF STRESS-INDUCED ANALGESIA 297
INTRODUCTION 297
CHARACTERISTICS OF OPIOID AND NONOPIOID FORMS OF STRESS-INDUCED ANALGESIA 297
ENDOCRINE PROCESSES MEDIATING STRESS-INDUCED ANALGESIA 298
ACKNOWLEDGEMENTS 299
REFERENCES 299
Chapter 86. ANTINOCICEPTIVE AND TOXIC ACTIVITIES OF INTRACEREBROVENTRICULARLY (ICV)ADMINISTERED MORPHINE (M) , 6-ACETYLMORPHINE (AM) AND 3,6-DIACETYLMORPHINE (DAM) IN MICE 300
INTRODUCTION 300
METHODS 300
RESULTS 301
DISCUSSION 302
REFERENCES 302
Chapter 87. POSSIBLE INVOLVEMENT OF INTRINSIC OPIOID PEPTIDES AND SEROTONIN IN PHENYLETHYLAMINE ANALOG-INDUCED ANALGESIA 303
SUMMARY 303
INTRODUCTION 303
METHODS 303
RESULTS 304
DISCUSSION 305
REFERENCES 305
Chapter 88. ANALGESIC PROPERTIES OF D-PHENYLALANINE, BACITRACIN AND PUROMYCIN IN MICE: RELATIONSHIP TO INHIBITION OF ENKEPHALINASE AND BETA ENDORPHINASE. 306
SUMMARY 306
INTRODUCTION 306
MATERIAIS AND METHODS 306
RESULTS 307
DISCUSSION 308
REFERENCES 308
Chapter 89. CHANGES IN ANTINOCICEPTION AFTER EXPOSURE OF ANIMALS DURING EARLY DEVELOPMENT TOCHRONIC STRESS AND CHRONIC ADMINISTRATION OF NARCOTIC ANALGESICS 309
SUMMARY 309
INTRODUCTION 309
METHODS 309
RESULTS 310
DISCUSSION 311
REFERENCES 311
Chapter 90. DYNORPHIN: DIFFERENTIAL INTERACTIONS WITH OPIATES AND PEPTIDES IN NAIVE AND MORPHINE TOLERANT MICE. 312
SUMMARY 312
INTRODUCTION 312
METHODS 312
RESULTS AND DISCUSSION 314
REFERENCES 314
Chapter 91. CENTRAL NOREPINEPHRINE IN ACUPUNCTURE ANALGESIA: DIFFERENTIAL EFFECTS IN BRAINAND SPINAL CORD 315
SUMMARY 315
INTRODUCTION 315
METHODS 315
RESULTS 316
DISCUSSION 317
REFERENCES 317
Chapter 92. AFFERENT AND EFFERENT PATHWAYS IN ACUPUNCTURE ANALGESIA AND THEIR CORRELATIONWITH MORPHINE ANALGESIA 318
SUMMARY 318
INTRODUCTION 318
METHODS 318
RESULTS 319
DISCUSSION 320
REFERENCES 320
Chapter 93. SUPPRESSION BY MORPHINE AND ACUPUNCTURE ON NOXIOUS INFORMATION IN THE RAT CENTRAL NERVOUS SYSTEM 321
SUMMARY 321
INTRODUCTION 321
METHODS 321
RESULTS 322
DISCUSSION 322
REFERENCES 323
CHAPTER 94. PARALLEL INDIVIDUAL VARIATIONS IN EFFECTIVENESS OF ACUPUNCTURE, MORPHINE ANALGESIA AND DORSAL PAG-SPA AND THEIR ABOLITION BY D-PHENYLALANINE 324
SUMMARY 324
INTRODUCTION 324
METHODS 324
RESULTS 324
DISCUSSION 325
REFERENCES 326
CHAPTER 95. THE ROLE OF CENTRAL 5-HYDROXYTRYPTAMINE IN ACUPUNCTURE ANALGESIA AND ACUPUNCTURE TOLERANCE 327
SUMMARY 327
INTRODUCTION 327
METHODS 327
RESULTS AND DISCUSSIONS 328
REFERENCES 329
CHAPTER 96. CENTRAL NOREPINEPHRINE: ITS IMPLICATION IN THE DEVELOPMENT OF ACUPUNCTURE TOLERANCE 330
SUMMARY 330
INTRODUCTION 330
METHODS 330
RESULTS AND DISCUSSIONS 331
REFERENCES 332
CHAPTER 97. Aß NERVE IMPULSE PRODUCES ELECTROACUPUNCTURE ANALGESIA IN RATa 333
SUMMARY 333
INTRODUCTION 333
METHODS 333
RESULTS 334
DISCUSSION 335
REFERENCES 335
CHAPTER 98. ACUPUNCTURE SUPPRESSES THE JAW OPENING REFLEX RELATED TO NOXIOUS INPUT IN RAT 336
SUMMARY 336
INTRODUCTION 336
METHODS 336
RESULTS 337
DISCUSSION 338
REFERENCES 338
CHAPTER 99. EFFECTS OF ELECTROACUPUNCTURE ON THE LEVELS OF ENDORPHIMS AND SUBSTANCE P IN HUMAN LUMBAR CSF. 339
SUMMARY 339
INTRODUCTION 339
METHODS 339
RESULTS 340
DISCUSSION 340
REFERENCES 341
CHAPTER 100. CSF ENDORPHIN LEVELS IN CHRONIC PAIN PATIENTS AND IN PATIENTS BEFORE AND AFTER APLACEBO PAIN RELIEF 342
SUMMARY 342
INTRODUCTION AND METHODS 342
RESULTS 343
DISCUSSION 344
REFERENCES 344
CHAPTER 101. ß-ENDORPHIN IN OBSTETRIC ANALGESIA 345
SUMMARY 345
INTRODUCTION 345
MATERIAL AND METHODS 345
RESULTS 346
REFERENCES 347
CHAPTER 102. DESCENDING INHIBITION IN HUMAN SPINAL CORD 348
SUMMARY 348
INTRODUCTION 348
METHODS 348
RESULTS 349
DISCUSSION 350
REFERENCES 350
PART VIII: BEHAVIORAL AND CLINICAL STUDIES 352
CHAPTER 103. NEUROLEPTIC-LIKE AND ANTI-PSYCHOTIC ACTION OF .-TYPE ENDORPHINS 353
SUMMARY 353
INTRODUCTION 353
INTERACTION BETWEEN DE.E AND APOMORPHINE 354
POSSIBLE MODE OF ACTION OF .-TYPE ENDORPHINS 354
REFERENCES 355
CHAPTER 104. MULTI-DIMENSIONAL ANALYSES OF BEHAVIOR IN MICE TREATED WITH ENDORPHINS 356
SUMMARY 356
INTRODUCTION 356
MATERIALS AND METHODS 356
RESULTS 357
DISCUSSION 357
ACKNOWLEDGEMENT 358
REFERENCES 358
CHAPTER 105. EFFECTS OF OPIOID DRUGS ON ACTIVE AVOIDANCE BEHAVIOR OF THE RAT 359
SUMMARY 359
INTRODUCTION 359
METHODS 359
RESULTS 360
DISCUSSION 361
REFERENCES 361
CHAPTER 106. BEHAVIORAL EFFECTS OF PROLACTIN: INVOLVEMENT OF OPIOID RECEPTORS 362
SUMMARY 362
INTRODUCTION 362
METHODS 362
RESULTS 363
DISCUSSION 364
REFERENCES 364
CHAPTER 107. INTERACTION BETWEEN MORPHINE AND PHENCYCLIDINE: INTOXICATION AND CROSS-TOLERANCE 365
SUMMARY 365
INTRODUCTION 365
METHODS 366
RESULTS 366
DISCUSSION 367
ACKNOWLEDGMENTS 367
REFERENCES 367
CHAPTER 108. ENKEPHALINERGIC MODULATION OF CIRCLING BEHAVIOUR INDUCED BY DOPAMINE IN THENUCLEUS ACCUMBENS AND NUCLEUS CAUDATUS 368
SUMMARY 368
INTRODUCTION 368
METHODS 369
RESULTS 369
DISCUSSION 370
REFERENCES 370
CHAPTER 109. EXOGENOUS OPIOIDS AND DRINKING AND FEEDING 371
SUMMARY 371
INTRODUCTION 371
REGULATION OF WATER INTAKE 371
FEEDING AND PALATABILITY 372
REFERENCES 373
CHAPTER 110. UNUSUAL BEHAVIORAL PROPERTIES OF SOME NEW OPIOID PEPTIDES 374
SUMMARY AND INTRODUCTION 374
METHODS 374
RESULTS AND DISCUSSION 374
REFERENCES 376
CHAPTER 111. 
377 
INTRODUCTION 377
CLINICAL INVESTIGATIONS 377
ACKNOWLEDGEMENT 379
REFERENCES 379
CHAPTER 112. NALOXONE REVERSES INDUCED ISCHEMIC NEUROLOGIC DEFICIT IN GERBILS 380
SUMMARY 380
INTRODUCTION 380
METHODS AND RESULTS 380
DISCUSSION 382
REFERENCES 382
CHAPTER 113. NALTREXONE AND PSYCHOTHERAPY 383
SUMMARY 383
INTRODUCTION 383
METHODS 383
RESULTS 384
DISCUSSION 385
REFERENCES 385
ACKNOWLEDGMENTS 385
CHAPTER 114. PATIENT CONTROL OF METHADONE MAINTENANCE DOSE 386
INTRODUCTION 386
METHODS 386
RESULTS 387
REFERENCES 388
ACKNOWLEDGEMENTS 388
CHAPTER 115. LAAM INSTEAD OF TAKE-HOME METHADONE 389
INTRODUCTION 389
METHODS 389
RESULTS 389
CONCLUSIONS 390
REFERENCES 390
CHAPTER 116. EFFECTS OF CHRONIC EXOGENOUS OPIOID ADMINISTRATION ON LEVELS OF ONE ENDOGENOUS OPIOID (ß-ENDORPHIN) IN MAN 391
SUMMARY 391
INTRODUCTION 391
METHODS 391
RESULTS 392
DISCUSSION 392
REFERENCES 392
CHAPTER 117. NALOXONE AND THYROTROPIN RELEASING HORMONE HAVE ADDITIVE EFFECTS IN REVERSING ENDOTOXIC SHOCK* 394
SUMMARY 394
INTRODUCTION 394
METHODS 394
RESULTS 395
DISCUSSION 396
REFERENCES 396
CHAPTER 118. THE ROLE OF ENKEPHALINS IN BLOOD PRESSURE IN THE BRAIN 397
SUMMARY 397
INTRODUCTION 397
METHODS 398
RESULTS 398
DISCUSSION 398
REFERENCES 399
PART IX: STRUCTURE-ACTIVITY RELATIONSHIPS OF OPIOIDS 400
CHAPTER 119. ACTIVE SITES IN THE ß-ENDORPHIN STRUCTURE FOR ACTIVATION OF THE EPSILON-OPIATERECEPTOR 401
SUMMARY 401
INTRODUCTION 401
EXPERIMENTAL PROCEDURES 401
RESULTS 401
DISCUSSION 402
ACKNOWLEDGEMENTS 403
REFERENCES 403
CHAPTER 120. CRITICAL COMPONENTS OF OPIOID PEPTIDES FOR SPECIFIC RECOGNITION OF µ AND d RECEPTORS 404
SUMMAR 404
INTRODUCTION 404
MATERIALS AND METHODS 404
RESULTS AND DISCUSSION 405
CONCLUS ION 406
REFERENCES 406
CHAPTER 121. HIGHLY ACTIVE DIPEPTIDE AND TRIPEPTIDE ENKEPHALIN ANALOGS 407
SUMMARY 407
INTRODUCTION 407
METHODS 407
RESULTS 408
DISCUSSION 409
REFERENCES 409
CHAPTER 122. TWO NEW CLASSES OF CYCLIC ENKEPHALIN ANALOGS WITH HIGH POTENCY AND SPECIFICITY FOR µ-RECEPTORS 410
SUMMARY 410
INTRODUCTION 410
RESULTS AND DISCUSSION 410
ACKNOWLEDGEMENTS 412
REFERENCES 412
CHAPTER 123. "MINIMAL SEGMENT" OF ENKEPHALIN FOR ANALGESIA: SYNDYPHALIN (SD)-33, A SIMPLE TRIPEPTIDE ALKYLAMIDE WITH PROLONGED SUBCUTANEOUS ANALGESIC ACTIVITY 413
SUMMARY 413
INTRODUCTION 413
MATERIALS & METHODS
RESULTS & DISCUSSION
REFERENCES 415
CHAPTER 124. THE ANALGESIC EFFECTS OF CYCLIC DIPEPTIDES BY INTRACEREBRAL ADMINISTRATION IN CONSCIOUS MICE AND RATS 416
SUMMARY 416
INTRODUCTION 416
METHODS 417
RESULTS 417
DISCUSSION 418
REFERENCES 418
CHAPTER 125. SYNTHETIC OPIOID a-CASEIN PEPTIDES. STRUCTURE ACTIVITY RELATIONSHIP 419
SUMMARY 419
INTRODUCTION 419
METHODS 420
RESULTS 420
DISCUSSION 421
REFERENCES 422
CHAPTER 126. SOME STRUCTURE-ACTIVITY RELATIONSHIPS IN THE 2I-MERCAPTOBENZOMORPHAN SERIES 423
SUMMARY 423
INTRODUCTION 423
SYNTHESIS 423
METHOD 424
RESULTS AND DISCUSSION 424
CHAPTER 127. CHEMICAL STRUCTURE AND PHARMACOLOGICAL ACTIVITIES OF DIPHENYLETHYLPIPERAZINE DERIVATIVES 426
SUMMARY 426
INTRODUCTION 426
METHODS 426
RESULTS 427
DISCUSSION 428
REFERENCES 428
CHAPTER 128. PERIPHERAL SELECTIVITY OF QUATERNARY NARCOTIC ANTAGONISTS:RELATIVE ABILITY TO PREVENT GASTROINTESTINAL TRANSIT INHIBITION AND ANTINOCICEPTION IN MORPHINIZED RATS.a) 429
SUMMARY 429
INTRODUCTION 429
METHODS 429
RESULTS AND DISCUSSION 431
REFERENCES 431
CHAPTER 129. STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF AFFINITY LABELS THAT ARE SPECIFICFOR µ OPIOID RECEPTORS 432
SUMMARY 432
INTRODUCTION 432
METHODS 432
RESULTS 433
DISCUSSION 433
REFERENCES 434
CHAPTER 130. ARYLAZIDO-DERIVATIVES OF 14ß-AMINOMORPHINONE : POTENTIAL PHOTOAFFINITY LIGANDSFOR OPIATE RECEPTORS 435
SUMMARY 435
METHODS 435
RESULTS AND DISCUSSION 437
REFERENCES 437
CHAPTER 131. ANTAGONIST-AGONIST ACTIVITY OF SOME N-SUBSTITUTED BENZOMORPHANS 438
SUMMARY 438
INTRODUCTION 438
METHOD 438
RESULTS AND DISCUSSION 439
CHAPTER 132. THE ACTION OF 2-AMINOTETRALIN (2-AT) DERIVATIVES ON HUMAN PLASMA CHOLINESTERASE(HPC) 441
SUMMARY 441
INTRODUCTION 441
METHODS 442
RESULTS 442
DISCUSSION 443
REFERENCES 443
CHAPTER 133. HOW QUANTUM CHEMISTRY CAN DELINEATE THE DIFFERING MOLECULAR REQUISITES FORINTERACTION WITH µ, d, ., s AND OTHER OPIATE RECEPTORS 444
SUMMARY 444
DISCUSSION 444
REFERENCES 446
PART X: TOLERANCE AND PHYSICAL DEPENDENCE 448
CHAPTER 134. OPIATE AND CLONIDINE DEPENDENCE IN THE FINAL CHOLINERGIC MOTONEURONE OF THEGUINEA-PIG ISOLATED ILEUM 449
SUMMARY 449
INTRODUCTION 449
OPIATE DEPENDENCE IN THE MYENTERIC PLEXUS 449
CLONIDINE DEPENDENCE IN THE FCMN 450
RATE OF OPIATE DEPENDENCE INDUCTION 451
REFERENCES 451
CHAPTER 135. CROSS-TOLERANCE AND CROSS-DEPENDENCE ON MULTIPLE OPIATE RECEPTORS OF THE GUINEAPIG ILEUM 452
SUMMARY 452
INTRODUCTION 452
METHODS 452
RESULTS 453
DISCUSSION 454
REFERENCES 454
CHAPTER 136. PROPERTIES OF OPIATE RECEPTOR BINDING IN AN OPIATE TOLERANT STATE 455
SUMMARY 455
INTRODUCTION 455
METHODS 455
RESULTS 456
DISCUSSION 457
REFERENCES 457
CHAPTER 137. IMPORTANCE OF OPIATE RECEPTORS OF THE SUBSTANTIA GELATINOSA TO MORPHINETOLERANCE AND DEPENDENCE OF CAT DORSAL HORN NEURONES 458
SUMMARY 458
INTRODUCTION 458
METHODS 458
RESULTS AND DISCUSSION 458
REFERENCES 460
CHAPTER 138. TOLERANCE TO ELECTROACUPUNCTURE AND ITS CROSS TOLERANCE TO MORPHINE 461
SUMMARY 461
INTRODUCTION 461
METHODS 461
RESULTS 462
DISCUSSION 463
REFERENCES 463
CHAPTER 139. ACUPUNCTURE AND MORPHINE ANALGESIA INHIBITORY SYSTEMS AND ITS CORRELATION WITHMORPHINE TOLERANCE 464
SUMMARY 464
INTRODUCTION 464
METHODS 464
RESULTS 464
DISCUSSION 466
REFERENCES 466
CHAPTER 140. PHOSPHORYLATION OF STRIATAL SYNAPTIC PLASMA MEMBRANE PROTEINS FROM MORPHINETOLERANTRATS 467
SUMMARY 467
INTRODUCTION 467
METHODS 468
RESULTS 468
CONCLUSION 468
REFERENCES 469
CHAPTER 141. PHYSICAL DEPENDENCE LIABILITY OF TETRAPEPTIDE ACYLHYDRAZIDE ANALOGS OF ENKEPHALIN IN RATS 470
SUMMARY 470
INTRODUCTION 470
METHODS 470
RESULTS 471
DISCUSSION 472
REFERENCES 472
CHAPTER 142. NAL0X0NE REVERSIBLE EFFECT OF MORPHINE ON SUBSTANCE P NEURONS IN THE RAT SPINALCORD 473
SUMMARY 473
INTRODUCTION 473
METHODS 473
RESULTS 474
DISCUSSION 475
REFERENCES 475
CHAPTER 143. INVOLVEMENT OF GABA IN THE ACUTE AND CHRONIC EFFECTS OF MORPHINE: NOCICEPTIVE GABA RELEASE AND RECEPTOR BINDING STUDIES 476
SUMMARY 476
INTRODUCTION 476
METHODS 477
RESULTS AND DISCUSSION 477
ACKNOWLEDGMENTS 478
REFERENCES 478
CHAPTER 144. THE INVOLVEMENT OF BRAIN HISTAMINERGIC MECHANISMS IN THE WITHDRAWAL PHASE OF MORPHINE DEPENDENCE 479
SUMMARY 479
INTRODUCTION 479
METHODS 479
RESULTS 480
DISCUSSION 481
REFERENCES 481
CHAPTER 145. A POTENTIATION OF PHYSICAL DEPENDENCE BY 6-CONJUGATION OF MORPHINE AND NALORPHINE 482
SUMMARY 482
INTRODUCTION 482
METHODS 482
RESULTS 482
DISCUSSION 484
REFERENCES 484
CHAPTER 146. TRANSPORT AND BINDING IN VIVO OF 3H-NALOXONE IN BRAINS OF MORPHINE DEPENDENTAND WITHDRAWN MICE 485
SUMMARY 485
INTRODUCTION 485
METHODS 485
RESULTS 486
DISCUSSION 487
REFERENCES 487
CHAPTER 147. INHIBITION OF TOLERANCE TO HUMAN BETA ENDORPHIN BY A LINEAR AND A CYCLIC PEPTIDE 488
SUMMARY 488
INTRODUCTION 488
METHODS 488
RESULTS 489
DISCUSSION 489
ACKNOWLEDGEMENT 490
REFERENCES 490
CHAPTER 148. DIFFERENTIAL EFFECTS OF THYROLIBERIN ON TOLERANCE TO THE ANALGESIC AND HYPOTHERMICEFFECTS OF MORPHINE IN MICE 491
SUMMARY 491
INTRODUCTION 491
METHODS 492
RESULTS 492
DISCUSSION 493
ACKNOWLEDGEMENT 493
REFERENCES 493
CHAPTER 149. INDUCTION OF PHYSICAL DEPENDENCE IN RATS BY SHORT TREATMENT OF MORPHINE-ADMIXED FOOD 494
SUMMARY 494
INTRODUCTION 494
METHODS 494
RESULTS 495
DISCUSSION 495
REFERENCES 495
CHAPTER 150. TOLERANCE AS THE ONLY SIGN OF WITHDRAWAL IN OPIATE DEPENDENT CHICK FETUSES 496
SUMMARY 496
INTRODUCTION 496
METHODS 496
RESULTS 497
DISCUSSION 498
REFERENCES 498
CHAPTER 151. CAFFEINE ENHANCES MORPHINE DEPENDENCE IN HUMANS 499
SUMMARY 499
INTRODUCTION 499
METHODS 499
RESULTS 500
DISCUSSION 501
REFERENCES 501
CHAPTER 152. SCHEDULE INDUCED SELF INJECTION OF HEROIN: DOSE RESPONSE RELATIONSHIPS 502
SUMMARY 502
INTRODUCTION 502
MATERIALS AND METHODS 503
RESULTS AND DISCUSSION 503
REFERENCES 504
CHAPTER 153. OPIATE DETOXIFICATION USING LOFEXIDINE 505
SUMMARY 505
INTRODUCTION 505
METHODS 505
RESULTS 506
DISCUSSION 506
REFERENCES 507
ACKNOWLEDGEMENTS 507
CHAPTER 154. DETECTION OF M0RPHINONE AS A NEW METABOLITE OF MORPHINE IN GUINEA PIG URINE 508
SUMMARY 508
INTRODUCTION 508
METHOD 508
RESULTS 509
DISCUSSION 510
REFERENCES 510
CHAPTER 155. KETAMINE-LIKE DISCRIMINATIVE CHARACTERISTICS OF THE STEREOISOMERS OFMETAZOCINE, CTCLAZOCINE, AND SKF 10,047 IN RHESUS MONKEYS 511
SUMMARY 511
IMTODUCTION 511
METHODS 512
RESULTS 512
DISCUSSION 512
REFERENCES 513
CHAPTER 156. CONCLUDING REMARKS 514
Author Index 518