Biochemical Studies of CNS Receptors

ISBN-13: 9781468443639 / Angielski / Miękka / 2012 / 436 str.

Leslie Iversen

Opis

It is now eight years since the first Handbook volumes on Basic Neuro- pharmacology were published, and there have been many important advances. As in many other areas in science, progress in this field has depended to a considerable extent on the availability of new experimental methods, and Volume 15 reviews some major recent developments, including new autoradiographic techniques that allow direct visualization of drug and transmitter receptors in the nervous system, and the pin- pointing of the precise locations of the changes in brain metabolism elicited by various drug treatments. Volume 16 and 17 cover two of the most active areas for basic research in psychopharmacology at the moment: the characterization of drug and transmitter receptors in brain by radioligand binding techniques, and studies of the role of small peptides in brain function. The latter area, in particular, illustrates how rapidly progress continues to be made in basic research on the mechanisms of chemical communication within the nervous system. Eight years ago when the Handbook first appeared none of the opioid peptides (enkephalins and endorphins) had yet been identified. Since then a whole new area of basic biological research has focused on these substances, and in addition we know of more than thirty other neuropeptides with putative eNS trans- mitter functions.

Spis treści

1 Molecular Aspects of Neurotransmitter Receptors: An Overview.- 1. Receptor Recognition: Ion and Nucleotide Regulation Associated with “Second Messengers”.- 2. Solubilized and Purified Receptors Clarify Synaptic Mechanisms.- 3. Neurotransmitter Uptake Receptors.- 4. References.- 2 Opiate Receptors.- 1. Introduction.- 2. Scope and Limitations of Methods.- 2.1. Pharmacological Methods in Vitro and in Vivo.- 2.2. Biochemical Methods; Binding Assays in Vivo and in Vitro.- 2.3. Histochemical Methods.- 3. Heterogeneity of Opiate Receptors.- 3.1. Evidence Based on Pharmacological Assays.- 3.2. Binding Assays.- 3.3. Selective Protection Assays.- 3.4. Effects of Irreversible Agonists and Antagonists.- 4. Distribution of Opiate Receptors.- 4.1. Central Nervous System.- 4.2. Peripheral Nervous System.- 4.3. Cultured Cells.- 4.4. Subcellular Distribution.- 4.5. Ontogenetic and Phylogenetic Variations.- 5. Properties of the Opiate Binding Sites.- 5.1. Physicochemical Properties.- 5.2. Effects of Ions.- 5.3. Effects of Nucleotides.- 6. Isolation of Opiate Receptors.- 6.1. Inactive Ligand-Macromolecular Complexes.- 6.2. Solubilized Macromolecules to Which Opioid Ligands Bind.- 7. Assessment of the Pharmacological and Binding Properties of Narcotic Analgesic Drugs.- 8. Excitation Effector Coupling.- 9. Changes in Binding Sites Induced by Drugs or Pathological Conditions.- 10. References.- 3 CNS Dopamine Receptors.- 1. Introduction.- 2. Dopaminergic Agonists and Antagonists and Their Actions.- 3. Anatomy.- 4. Pharmacological Characterization of Dopamine Receptors.- 4.1. The “D-l” Dopamine Receptor and the Dopamine-Sensitive Adenylate Cyclase.- 4.2 “D-2” Dopamine Receptors.- 5. Dopamine Receptors in the Pituitary.- 6. Dopamine Receptors in the Striatum.- 6.1. Studies with Competitive Ligand s.- 7. Irreversible Modification of Dopamine Receptors.- 7.1. Phenoxybenzamine: Selective Alkylation of [3H]- Butyrophenone Binding Sites.- 7.2. A Chloroethylnorapomorphine: Effects on [3H]- NPA Binding and Dopamine-Receptor-Mediated Behavior.- 7.3. Heat Treatment: Multiple Effects Mimicking GTP.- 8. Solubilization and Isolation of Dopamine Receptors Ill.- 9. Neuroanatomical Localization of Dopamine Receptors in the CNS.- 5. Neostriatum.- 6. Substantia Nigra.- 7. Retina.- 1. Regulation of Dopamine Receptors.- 1.1. Up Regulation.- 1.2. Down Regulation.- 2. Concluding Comments.- 3. References.- 4 5-Hydroxytryptamine Receptors in Brain.- 1. Introduction.- 2. Serotoninergic Recognition Sites in the CNS.- 2.1. Neuronal Binding Sites.- 2.2. Glial Binding Sites.- 2.3. Multiple Serotonin Receptors.- 3. 5-HT-Sensitive Adenylate Cyclase.- 3.1. Neuronal 5-HT-Sensitive Adenylate Cyclase.- 3.2. Glial 5-HT-Sensitive Adenylate Cyclase.- 4. Mechanism of Regulation of Serotonin Receptors.- 4.1. Regulation at the Binding Site.- 4.2. Regulation of 5-HT-Sensitive Adenylate Cyclase Activity.- 4.3. Proposed Mechanism of Regulation of the 5-HT Receptor.- 4.4. Effects of Antidepressant Drugs on the Postsynaptic Serotonin Receptor.- 5. Conclusions.- 6. References.- 5 Receptors for Amino Acid Transmitters.- 1. Introduction.- 1.1. Historical Review.- 1.2. Definitions.- 1.3. Neurophysiological Techniques.- 1.4. Radioligand Binding Studies.- 1.5. Isolated Tissue or Organ Techniques.- 2. GAB A Receptors.- 2.1. Historical Review.- 2.2. Separation of GAB A Receptors from Uptake.- 2.3. GABA Agonists.- 2.4. GABA Antagonists.- 2.5. Coupling of GABA Receptors to Cyclic Nucleotides.- 2.6. Presynaptic GABA Receptors.- 2.7. Unusual Responses to GABA.- 2.8. Other GABA-Related Drugs.- 2.9. GABA Receptor Autoradiography.- 2.10. Complex Interactions between GABA, Benzodiazepines, and Barbiturates.- 2.11. Developmental Studies of GABA Receptors.- 2.12. Desensitization.- 2.13. GABA Agonists and Seizures.- 2.14. GABA Receptors and Human Disease.- 2.15. Radioreceptor Assays.- 3. Glycine Receptors.- 3.1. Historical Review.- 3.2. Glycine Effects and Glycine Agonists.- 3.3. Glycine Antagonists.- 3.4. Glycine Receptor Autoradiography.- 3.5. Absence of Desensitization at Glycine Synapses.- 4. Other “Inhibitory Amino Acids”.- 5. Excitatory Amino Acids.- 6. Summary.- 7. References.- 6 The Nature of Muscarinic Receptor Binding.- 1. Introduction.- 2. The Binding of Antagonists.- 2.1. Pharmacological Uses of Competitive Antagonists.- 2.2. Characteristics of [3H]Antagonist Binding.- 2.3. Cellular Localization of [3H]Antagonist Binding.- 3. The Binding of Agonists.- 3.1. Characteristics of Agonist Binding.- 3.2. Explanations for the Complexities of Agonist Binding.- 3.3. Comparison of Agonist Binding with Pharmacological Responses.- 4. Regulation of Muscarinic Receptors by Guanine Nucleotides.- 4.1. Introduction.- 4.2. Regulation of Agonist Binding by Guanine Nucleotides.- 4.3. Regulation of [3H]Antagonist Binding by Guanine Nucleotides.- 5. The Influence of Sulfhydryl Reagents on Muscarinic Receptor Binding.- 6. Ionic Perturbation of Muscarinic Receptor Binding.- 7. Regulation of Antagonist Binding by Dopaminergic Agonists.- 8. Conclusion.- 9. References.- 7 Benzodiazepine Receptors.- 1. Introduction.- 2. Biochemical Characteristics of Benzodiazepine Receptor Binding.- 2.1. [3H]Benzodiazepine Radioligands.- 2.2. Nonbenzodiazepine Radioligands.- 2.3. Binding Thermodynamics.- 3. BZ Receptor Solubilization.- 4. Occurrence of BZ Receptors.- 4.1. Brain versus Periphery.- 4.2. Neuronal Localization.- 4.3. Brain Distribution.- 4.4. Ontogenesis and Phylogenesis.- 5. Structural Selectivity of BZ Receptors.- 5.1. Benzodiazepines.- 5.2. Nonbenzodiazepine Inhibitors.- 5.3. Ineffective Agents.- 6. BZ Receptor Binding in Vivo.- 6.1. Methodological Considerations.- 6.2. Structural Selectivity.- 7. Multiple Brain BZ Receptors.- 8. BZ Receptors and GABA.- 8.1. Physiology and Pharmacology.- 8.2. GABAergic Influence on BZ Receptors.- 8.3. Benzodiazepine Effects on GABA Receptors.- 8.4. Barbiturates, Chloride Channels, and BZ Receptors.- 8.5. Benzodiazepine Receptor/GABA Receptor/ Chloride Channel Complex.- 8.6. Pharmacological Efficacy of BZ Receptor Ligand s; Relation to GABA.- 9. Miscellaneous Modulators.- 10. In Vivo BZ Receptor Modulation.- 10.1. Subchronic Treatment with Benzodiazepines.- 10.2. Barbiturates.- 10.3. Ethanol.- 10.4. Diphenylhydantoin.- 10.5. Seizures and Other “Stress”.- 11. Endogenous Ligands?.- 11.1. ß-Carbolines.- 11.2. Purines 363 l.- 11.3. Nicotinamide.- 11.4. Miscellaneous Agents and Extracts.- 12. Radioreceptor Assay.- 13. References.- 8 Histamine Receptors in Brain.- 1. Introduction.- 2. Classification of Histamine Receptors.- 3. The Histamine Hi-Receptor.- 3.1. The Hi-Receptor Characterized by Binding Studies.- 3.2. The HrLinked Guanylate Cyclase.- 3.3. The Hi-Linked Adenylate Cyclase.- 4. The Histamine H2-Receptor.- 5. Psychotropic Drugs and Histamine Receptors.- 5.1. Antidepressant Drugs.- 5.2. Neuroleptic Drugs.- 5.3. Hallucinogenic Substances.- 5.4. Concluding Comment.- 6. References.