Receptors (eBook)

Front Cover 1
Receptors 4
Copyright Page 5
Table of Contents 6
Introduction 9
Part 1: Opiate Receptors and Their Endogenous Ligands 11
Chapter 1. Chemistry and Biochemistry of Pituitary Endorphins 13
ABSTRACT 13
INTRODUCTION 13
STRUCTURAL REQUIREMENTS FOR ANALGESIC EFFECT 13
PROTEINASES INVOLVED IN THE GENERATION OF PITUITARY ENDORPHINS 17
REFERENCES 21
Chapter 2. Multiple Opiate Receptors 25
INTRODUCTION 25
INTERACTIONS OF OPIATES AND ENDOGENOUS OPIOID PEPTIDES WITH OPIATE RECEPTORS 25
PHARMACOLOGICAL PATTERN OF ENKEPHALIN ANALOGUES 27
POSSIBLE PHYSIOLOGICAL SIGNIFICANCE 28
SUMMARY 31
ACKNOWLEDGEMENTS 31
REFERENCES 31
Chapter 3. Pituitary Endorphins: Recent Progress 35
Abstract. 35
Slow-Reversing Endorphin A Different Pituitary Opioid Peptide
Role of the Pituitary in the Hyperalgesic Effect of Naloxone. 37
Acknowledgements. 38
References. 38
Chapter 4. The Biosynthesis and Releaseof the Enkephalins 41
INTRODUCTION 41
RELEASE OF ENKEPHALINS 42
BIOGENESIS OF ENKEPHALINS 44
CONCLUDING REMARKS 45
Acknowledgements 46
REFERENCES 46
Chapter 5. Opiate Receptors: A) Functional Heterogeneity Demonstrated with an Apparently Irreversible Naloxone Derivative: B) Regulation by Guanine Nucleotides 49
ABSTRACT 49
KEYWORDS 49
Naloxazine Influences Upon Opiate Receptor Binding and Analgesia: 50
REFERENCES 55
Chapter 6. Opiate Receptors, Their Endogenous Ligands and the Development of Tolerance/Dependence 57
ABSTRACT 57
INTRODUCTION 57
I. Changes at the Receptor Level 58
II. Chronic Opiate Actions and Endogenous Ligands 59
III. Manifestation of Opiate Tolerance/Dependence at the Single Neurone Level 62
IV. Concluding Remarks - Neuronal Sensitivity and Chronic Opiate Action 64
REFERENCES 64
Chapter 7. Physiological and Patho Physiological Relevance of the Endogenous Ligands of the Opiate Receptors 67
ABSTRACT 67
INTRODUCTION 67
INTEGRATED FUNCTION 68
INTERACTION BETWEEN ENDOGENOUS LIGANDS OF OPIATE RECEPTORS AND OTHER HORMONES, MEDIATORS OR MODULATORS 73
PATHOLOGICAL STATES 74
CONCLUSIONS 75
AKNOWLEDGMENTS 75
REFERENCES 75
Part 2: Membrane Receptors in Eucaryotic Cells 81
Chapter 8. Multiple Classes of Muscarinic Receptor Binding Sites in the Brain 83
REFERENCES 55
Chapter 9. Opiate Receptors, Their Endogenous Ligands and the Development of Tolerance/Dependence 57
ABSTRACT 57
INTRODUCTION 57
I. Changes at the Receptor Level 58
II. Chronic Opiate Actions and Endogenous Ligands 59
III. Manifestation of Opiate Tolerance/Dependence at the Single Neurone Level 62
IV. Concluding Remarks - Neuronal Sensitivity and Chronic Opiate Action 64
REFERENCES 64
Chapter 10. Physiological and Pathophysiological Relevance of the Endogenous Ligands of the Opiate Receptors 67
ABSTRACT 67
INTRODUCTION 67
INTEGRATED FUNCTION 68
INTERACTION BETWEEN ENDOGENOUS LIGANDS OF OPIATE RECEPTORS AND OTHER HORMONES, MEDIATORS OR MODULATORS 73
PATHOLOGICAL STATES 74
CONCLUSIONS 75
AKNOWLEDGMENTS 75
REFERENCES 75
Part 3: Membrane Receptors in Eucaryotic Cells 81
Chapter 11. Multiple Classes of Muscarinic Receptor Binding Sites in the Brain 83
ABSTRACT 83
REFERENCES 89
Chapter 12. Biophysical Aspects of Agonist Action at Frog Endplate 91
INTRODUCTION 91
FLUCTUATION AND RELAXATION TECHNIQUES 91
SIMPLE MOLECULAR MODELS 93
CONCENTRATION DEPENDENCE OF CHANNEL KINETICS 94
DECAMETHONIUM BOTH OPENS AND BLOCKS CHANNELS 97
REFERENCES 99
Chapter 13. Some Observations on Denervation Supersensitivity in Skeletal Muscle 101
INTRODUCTION 101
RESULTS AND DISCUSSION 101
REFERENCES 106
Chapter 14. Structural and Functional Properties of the Acetylcholine-Regulator 109
I - STRUCTURE OF THE ACh-REGULATQR IN ACh-RECEPTQR RICH MEMBRANE FRAGMENTS 109
II - ALLOSTERIC INTERACTION BETWEEN AChR AND I0N0PH0RE IN AChR-RICH MEMBRANE FRAGMENTS 111
Ill - ISOLATION OF A PROTEIN CARRYING THE LOCAL ANESTHETIC BINDING SITE AND RECONSTITUTION OF A FUNCTIONAL ACh-REGULATOR 113
IV - CONCLUSIONS 114
REFERENCES 114
Chapter 15. Glutamate Receptors in Eucaryotes 117
Evolutionary Comments 117
Structure/Activity Phenomena 118
Glutamate Receptor Populations on Locust Muscle 119
Glutamate Receptors on Denervated Locust Muscle 120
Desensitisation of Glutamate Receptors on Locust Muscle 123
Concanavalin A and Glutamate Receptors on Locust Muscle 123
Glutamate Antagonist 123
Conclusion 124
References 124
Chapter 16. Biochemistry and Physiology of Dopaminergic and Beta-Adrenergic Receptors in Mammalian Central Nervous System 127
DOPAMINE RECEPTORS 127
Multiple Classes of Dopamine Receptors 127
Dopaminergic Ergots Distinguish Between Receptors. 128
Linkage of Dopamine Receptors to Adenylyl Cyclase 130
BETA-ADRENERGIC RECEPTOR IN THE BRAIN 131
Beta-Adrenergic Regulation of Brain Adenylyl Cyciase 133
Binding of 3H-Dihydroalprenolol to Cerebellar Homogenate 133
REFERENCES 135
Chapter 17. Beta-Adrenergic Receptors in C6 Glioma Cells and Central Nervous System 137
INTRODUCTION 137
RESULTS 137
CONCLUSION 144
REFERENCES 144
Chapter 18. Recent Studies on Opiate Receptors 147
DISCOVERY OF OPIATE RECEPTORS AND THEIR PROPERTIES 147
C0NF0RMATI0NAL STATES OF THE OPIATE RECEPTOR 147
THE ROLE OF PHOSPHOLIPIDS IN OPIATE RECEPTOR BINDING 149
A TISSUE CULTURE MODEL FOR THE STUDY OF OPIATE RECEPTORS 151
PROGRESS IN SOLUBILIZATION AND PURIFICATION OF OPIATE RECEPTORS 152
DISCOVERY OF ENDOGENOUS OPIOID PEPTIDES 153
CONCLUDING COMMENTS 154
REFERENCES 154
Chapter 19. The Role of Guanylnucleotides in the Regulation of Hormonally Stimulated Adenylate Cyclase 159
A GTP-BINDING PROTEIN IS PART OF THE ADENYLATE CYCLASE COMPLEX 159
ACKNOWLEDGEMENT 166
REFERENCES 166
Capter 20. Catecholamine-Sensitive Adenylate Cyclase: Identification and Partial Characterization of Some of its Components 169
INTRODUCTION 169
METHODS 170
RESULTS 170
CONCLUSIONS 179
REFERENCES 179
Chapter 21. Interactions of Cholera Toxin with Cell Membranes 181
BINDING OF CHOLERA TOXIN TO CELLS 182
PASSAGE OF SUBUNIT A THROUGH THE CELL MEMBRANE 183
ACTIVATION OF ADENYLATE CYCLASE BY FRAGMENT .1 185
REFERENCES 187
Chapter 22. Hybridization of Hormone Receptors with Adenylate Cyclase Systems of Different Cells 191
ABSTRACT 191
INTRODUCTION 192
EXPERIMENTAL AND DISCUSSION 192
CONCLUSIONS 196
Acknowledgements 196
REFERENCES 197
Chapter 23. Receptor Binding Studies of Beta-AdrenergicReceptors: New Insights into Activation and Desensitization of Adenylate Cyclase 199
REFERENCES 208
Part 4: Applications of Binding to Pharmacological Research 211
Chapter 24.Control of Hormone Receptor Levels and Function 213
INTRODUCTION 213
EFFECTS OF ESTROGENS ON TRH RECEPTOR LEVELS AND FUNCTION 213
AUTOREGULATION OF TRH RECEPTORS 215
INTERACTIONS OF SEX STEROIDS AND "INHIBIN" WITH LHRH RECEPTOR ACTION 215
AUTOREGULATION OF LHRH RECEPTORS 216
EFFECTS OF ESTROGENS ON PITUITARY DOPAMINE RECEPTORS AND FUNCTION 217
DOWN-REGULATION OF TESTICULAR AND OVARIAN RECEPTORS BY EN-DOGENOUS LH 219
REFERENCES 222
Cbhapter 25. Problems in Studying Hormone Receptor Binding 225
LABELED HORMONES 225
DISPLACEMENT CURVES 229
NON-SPECIFIC BINDING 229
REFERENCES 230
Chapter 26. Methodological Approach to Radioligand Binding Studies of Adrenergic Receptors 233
Radioligand 234
Tissue Preparations 235
Methods of Assaying Specific Radioligand Binding 236
Incubation Conditions 237
Specific and Non-Specific Binding 238
Potential Artifacts 239
REFERENCES 240
Part 5: Main Lectures 243
Chapter 27. Synaptic Receptor Proteolipids: Isolation and Molecular Biology 245
Proteolipids are involved in important membrane functions 246
Cholinergic proteolipids are separated by affinity chromatography in organics olvents. 248
The binding to the proteolipid is with the protein moiety and not with acidic lipids. 248
Receptor proteolipids for glutamate and GABA are present in artropod muscles. 249
Receptor proteolipids for amino acid neurotransmitters are present in the cerebral cortex of mammals. 251
The cholinergic proteolipid from the electroplax shows some similarities withthe proteodetergent. 253
The main protein band of the proteoiipid from Torpedo is about 39 Kdaltons 256
The ligand-proteolipid interaction can be studied by several physical methods 257
The ion-conducting mechanism is manifested by an in crease in membrane noise 258
The membrane "noise" may be observed in cholinergic proteolipid reconstituted in black lipid membranes. 259
A tentative model of the cholinergic receptor 263
REFERENCES 264
Chapter 28. The Mechanism of Action of Anti-Hormones 269
KINETICS OF THE INTERACTION WITH THE CYTOPLASMIC RECEPTOR 270
BIOLOGICAL ACTIVITY 274
ANTI-HORMONAL ACTIVITY 277
MULTIPLE EFFECTS OF ANTI-HORMONES 282
HYPOTHESES AND CONJECTURES 284
APPENDIX. Chemical names of the test-substances. 285
REFERENCES. 285
Chapter 29. Angiotensin Receptors 289
1. Angiotensin-receptor interaction. 289
2. Angiotensin III receptors in corticoadrenals. 295
3. Angiotensin receptor modulation. 296
References. 297
Index 301