This two-volume book provides the first comprehensive survey of opioid research, a field which has accumulated a tremendous amount of literature since the identification of opioid receptors and their endogenous ligands. In more than 60 chapters experts present state-of-the-art reviews of this fascinating field, the topics ranging from molecular biology to clinical applications. Part I covers the multiplicity of opioid receptors, the chemistry of opiates and opioid peptides as well as the neurophysiology of opioids. Part II reviews a broad spectrum of physiological and behavioral functions and pharmacological actions of opioids, together with their neuroendocrinology, opioid tolerance and dependence, concluding with pathophysiological aspects and clinical use.

Inhalt

Section A: Opioid Receptors/Multiplicity.- 1 Opioid Receptor Multiplicity: Isolation, Purification, and Chemical Characterization of Binding Sites.- A. Introduction.- B. Opioid Receptors Exist in Multiple Types.- C. Selective Ligands for the Major Types of Opioid Receptors.- D. Characterization of Membrane-Bound Opioid Receptor Types.- E. Putative Endogenous Ligands.- F. Separation and Purification of Opioid Binding Sites.- I. Solubilization.- II. Physical Separation.- III. Affinity Cross-Linking.- IV. Partial Purification.- V. Purification to Homogeneity.- G. Recent Studies on Purified ?-Opioid Binding Protein.- I. Antibodies Generated Against Peptide Sequences.- II. Rhodopsin Antibodies React with Purified OBP.- III. Attempts to Clone the cDNA of Purified OBP.- H. Concluding Comments.- References.- 2 Expression Cloning of cDNA Encoding a Putative Opioid Receptor.- A. Project History.- B. Expression Cloning.- I. Methodology.- II. Attempt by Stable Transfection.- III. Transient Transfection, Panning.- C. Ligand Binding by the Expressed Receptor.- D. Sequence Analysis, Structure of the Receptor.- E. Conclusions.- References.- 3 Characterization of Opioid-Binding Proteins and Other Molecules Related to Opioid Function.- A. Introduction.- B. cDNA Cloning.- I. Molecular Cloning of OBCAM.- II. Molecular Cloning and Characterization of Gene Products Downregulated by Chronic Opioid Treatment of NG108-15 Cells.- III. Use of Consensus Sequences in cDNA Cloning of Opioid Receptors.- C. Use of Antibodies to Characterize Opioid Receptors.- D. Antisense cDNA.- References.- 4 Use of Organ Systems for Opioid Bioassay.- A. Introduction.- I. Rationale for the Use of Isolated Organ Systems.- II. Tissue Preparations.- III. Applications of Peripheral Tissue Bioassay.- B. Measurement of Pharmacological Constants.- I. Theoretical Considerations.- 1. Determination of Agonist Affinity.- 2. Determination of Antagonist Affinity.- II. Methodological Considerations.- 1. Choise of Tissue Preparation.- 2. Tissue Preparation and Setup.- 3. Optimization of Equilibrium Conditions.- C. Assay Preparations.- I. Guinea Pig Ileum.- 1. ?-Receptors.- 2. ?-Receptors.- 3. ?-Receptors.- II. Mouse Vas Deferens.- 1. ?-Receptors.- 2. ?-Receptors.- 3. ?-Receptors.- III. Other Vasa Deferentia.- 1. Rat Vas Deferens.- 2. Hamster Vas Deferens.- 3. Rabbit Vas Deferens.- D. Conclusions.- References.- 5 Anatomical Distribution of Opioid Receptors in Mammalians: An Overview.- A. Introduction.- B. Anatomical Distributions.- I. ?-Receptors.- II. ?-Receptors.- III. ?-Receptors.- IV. Anatomical Conclusions.- C. Multiple ?-Receptor Subtypes.- D. Nigrostriatal and Mesolimbic Dopamine Systems as Models for Opioid Peptide and Receptor Interactions.- I. Conclusions.- E. Future Directions.- References.- 6 Opioid Receptor Regulation.- A. Introduction.- B. Regulation of Opioid Receptors in the Adult Brain by Chronically Administered Opioid Agonists and Antagonists.- I. Chronic Administration of Opioid Agonists In Vivo.- II. Chronic Administration of Agonists to Cells Grown in Culture.- III. Chronic Administration of Opioid Antagonists.- C. Regulation of Opioid Receptors by Other Drugs or Specific Brain Lesions.- D. Regulation of Opioid Receptor and Peptide Gene Expression in Embryonic and Neonatal Brain.- I. Effects of Chronic Opioid Administration on Opioid Receptor Expression.- 1. Perinatal Treatment.- 2. Postnatal Treatment.- II. Effects of Chronic Opioid Administration on Opioid Peptide Expression.- References.- 7 Multiple Opioid Receptors and Presynaptic Modulation of Neurotransmitter Release in the Brain.- A. Introduction.- B. Modulation of Noradrenaline Release.- C. Modulation of Acetylcholine Release.- D. Modulation of Dopamine Release.- E. Modulation of the Release of Other Neurotransmitters.- F. Conclusions.- References.- 8 Opioid Receptor-G Protein Interactions: Acute and Chronic Effects of Opioids.- A. Introduction.- B. Effects of Guanine Nucleotides on Ligand Binding to Opioid Receptors.- I. Opioid ?- and ?-Receptors Are Funtionally Linked to Guanine Nucleotide Binding Proteins.- 1. Guanine Nucleotides Lower Agnonist Affinity at ?- and ?-Receptors.- 2. Guanine Nucleotides Increase Agonist Dissociation Rates.- 3. Guanine Nucleotide Effects on Equilibrium Binding of Opioids.- 4. Sodium Regulates Agonist Affinity at ?- and ?-Receptors.- 5. Stimulation of GTPase Activity by Activation of ?- and ?-Receptors.- II. Evidence for ?-Receptor Interactions with G Proteins.- 1. Effects of Guanine Nucleotides on Agonist Binding at ?1-Sites.- 2. Effects of Guanine Nucleotides on Binding at ?2-Sites.- III. Stimulatory Effects of Opioids: Possible Interactions of Opioid Receptors with Gs.- C. Cellular Consequences of Sustained Exposure to Opiate Drugs.- I. Characteristics of Opioid Tolerance and Dependence.- II. Changes in the Number of Opioid Receptors Following Sustained Exposure to High Concentrations of Opiate Drugs.- 1. In Vitro Studies Employing Tissue Culture.- 2. Effects of Chronic Opioid Treatment in Brain.- 3. Effects of Chronic Treatment with ?-Agonists.- 4. Mechanisms Implicated in Changes in Receptor Site Density.- III. Chronic Opioid Treatment Uncouples Opioid Receptors from Their Associated G Proteins.- 1. Receptor Desensitization; ?- and ?-Receptors.- 2. Mechanisms Implicated in Receptor Desensitization.- IV. Sustained Opioid Exposure Induces Changes in the Cellular Concentrations of Some G Proteins.- 1. Neuroblastoma X Glioma (NG 108-15) Hybrid Cells.- 2. Guinea Pig Ileum Myenteric Plexus.- 3. Central Nervous System.- 4. Agonist Regulation of G Protein Levels.- V. Effector System Function May Be Enhanced After Sustained Opiate Drug Treatment.- 1. Guinea Pig Ileum Myenteric Plexus.- 2. Neuroblastoma X Glioma (NG 108-15) Hybrid Cells.- 3. Dorsal Root Ganglion-Spinal Cord Cultures.- 4. Locus Ceruleus.- 5. Summary.- VI. Summary: G Proteins and Opioid Tolerance and Dependence.- References.- 9 Opioid Receptor-Coupled Second Messenger Systems.- A. Introduction.- B. G Protein Coupling to Receptors.- I. General G Protein Structure and Function.- II. Opioid Receptors Are Coupled to G Proteins.- C. Opioid-Inhibited Adenylyl Cyclase.- I. Acute Effects of Opioid Agonists on Adenylyl Cyclase in Transformed Cell Lines.- II. Acute Effects of Opioid Agonists on Adenylyl Cyclase in Brain.- III. Chronic Effects of Opioid Agonists.- IV. Biological Roles for Opioid-Inhibited Adenylyl Cyclase.- D. Other Second Messenger Systems.- I. Stimulation of Adenylyl Cyclase.- II. Cyclic GMP.- III. Phosphatidylinositol Turnover and Effects on Membrane Lipids.- IV. Opioid-Dependent Protein Phosphorylation.- E. Conclusions.- References.- 10 Allosteric Coupling Among Opioid Receptors: Evidence for an Opioid Receptor Complex.- A. Introduction.- B. Evidence for a ?-?-Opioid Receptor Complex.- I. Ligand-Binding Data.- 1. Evidence that ?-Ligands Noncompetitively Inhibit ?-Receptor Binding.- 2. Evidence that ?-Ligands Noncompetitively Inhibit ?-Receptor Binding.- II. ?-Agonist - ?-Agonist Interactions.- 1. Early Studies: Analgesia Model.- 2. More Recent Studies: Analgesia Model.- III. ?-Antagonist - ?-Antagonist Interactions.- IV. Linkage Studies.- C. Evidence for…