The Serotonin Receptors

Serotonin (5-HT) was isolated and chemically characterized nearly four decades ago, and is now generally accepted to function as a neurotransmitter and neuromodulatory agent. Early research focused on the measurement of concentrations, synthesis, and metabolism of 5-HT, and only recently has the focus shifted to characterization of 5-HT receptors. Gaddum and Picarelli first sug­ gested in 1957 that the effect of 5-HT in the guinea pig ileum is mediated by two pharmacologically distinguishable receptors; however, the possibility of dual5-HT receptors was not explored systematically or successfully until the past decade. It is now clear that more, perhaps many more, subclasses of 5-HT receptors exist. The purpose of this book is to provide an up-to-date report on 5-HT receptors. This is a difficult task considering the astonishing speed at which research in this field is expanding. As the first of what we can expect to be a steady stream of monographs focusing on 5-HT receptors, the book confirms that we are in an exciting time in the history of 5-HT. For those of us who have been work­ ing on 5-HT for many years, our dream of equal progress and recognition with the more extensively studied catecholamines is finally being realized. We now have a Serotonin Club that held its first international scientific meeting in 1987, and several more international meetings are in the planning stages.

Contenu

Section 1: Historical Perspective.- 1 Historical Perspectives.- 1. The Discovery of 5-HT.- 2. Characterization of Serotonin Receptors.- 2.1. M and D Receptors.- 2.2. 5-HT1 and 5-HT2 Binding Sites.- 2.3. 5-HT3 Receptors.- 2.4. Neurophysiological Studies of 5-HT.- 2.5. 5-HT and Behavior.- 3. Future Approaches.- References.- Section 2: Characterization of Serotonin Receptor Binding Sites.- 2 Biochemistry and Pharmacology of the 5-HT1 Serotonin Binding Sites.- 1. Introduction.- 1.1. Historical Perspectives: The Origins of the 5-HT1 Binding Site Classification.- 1.2. Current Classification and Definitions of Subtypes of 5-HT1 Sites.- 2. Radioligand Binding Assays for 5-HT1 Sites.- 2.1. [3H]LSD Binding.- 2.2. [3H]5-HT Binding.- 2.3. 5-HT1 Subtype-Selective Radioligands.- 3. Pharmacology of 5-HT1 Binding Sites.- 4. Isolation and Purification of 5-HT1 Binding Site Subtypes.- 4.1. Solubilization of 5-HT1 Binding Sites.- 4.2. Affinity Labels for 5-HT1 Binding Sites.- 5. Summary.- References.- 3 Pharmacology and Biochemistry of the 5-HT2 Receptor.- 1. Introduction.- 2. Current Methods in Radioligand Binding Sites.- 3. Antagonist Radioligands for 5-HT2 Receptors.- 4. Agonist Radioligands for 5-HT2 Receptors.- 5. 5-HT2 Receptor: Site of Action of Hallucinogenic Drugs.- 6. Solubilization, Purification, and Reconstruction of 5-HT2 Receptors.- 7. Summary.- References.- 4 Autoradiographic Studies of Serotonin Receptors.- 1. Introduction.- 2. Ligands and Conditions for the Autoradiographic Localization of 5-HT Receptors in the Rat Brain.- 3. Characteristics of 5-HT Receptors in Rat Brain Examined Autoradiographically.- 4. Distribution of 5-HT Receptors in the Rat Brain.- 4.1. Distribution of 5-HT1 Receptors in Rat Brain.- 4.2. Distribution of 5-HT2 Receptors in Rat Brain.- 4.3. 5-HT3 Receptors: Apparent Absence from the Rat Brain.- 5. Lesion Studies and Possible Localization of 5-HT Sites in Specific Brain Pathways.- 5.1. Lesions of the Serotoninergic Pathways.- 5.2. Lesions of Chemically Identified Pathways: The Dopaminergic Nigrostriatal System.- 5.3. The Striatonigral Pathways.- 5.4. Cholinergic Pathways.- 5.5. Lesions of a Functional Pathway: 5-HT Receptors in the Visual System.- 6. Serotonin Receptors in Human Brain.- 6.1. 5-HT1 Receptors in Human Brain.- 6.2. 5-HT2 Receptors in Human Brain.- 7. Species Differences in Brain 5-HT Receptors: A Phylogenetic Approach.- 8. Conclusions and Future Trends.- References.- Section 3: Biochemical Mechanisms of Receptor Action.- 5 5-HT Receptors Coupled to Adenylate Cyclase.- 1. Introduction.- 2. Signal Transduction through G Protein Systems.- 3. Pharmacological Considerations.- 4. Increases in Cyclic AMP Production Induced by 5-HT.- 4.1. Invertebrate Tissues.- 4.2. Mammalian Nonneuronal Tissues.- 4.3. Mammalian Neuronal Tissues.- 5. Decreases in Cyclic AMP Production Induced by 5-HT.- 5.1. Inhibition of Basal or Receptor-Stimulated Cyclic AMP Production by 5-HT.- 5.2. 5-HT1A Receptor-Mediated Inhibition of Adenylate Cyclase.- 6. Possible Roles for Cyclic AMP in 5-HT Receptor Systems.- 6.1. Synapsin and Neurotransmitter Release.- 6.2. 5-HT, Cyclic AMP, and the GUI-Withdrawal Reflex in Aplysia.- 7. Summary and Conclusions.- References.- 6 5-HT Receptors Coupled to Phosphoinositide Hydrolysis.- 1. Introduction.- 2. 5-HT Stimulated Phosphoinositide Hydrolysis in Invertebrate Tissues.- 3. 5-HT Stimulated Phosphoinositide Hydrolysis in Mammalian Nonneuronal Tissues.- 3.1. Smooth Muscle Preparations.- 3.2. Platelets.- 3.3. Choroid Plexus.- 4. 5-HT Stimulated Phosphoinositide Hydrolysis in Mammalian Neuronal Tissues.- 4.1. Cerebral Cortex.- 4.2. Cultured Cells.- 4.3. Other Brain Regions.- 5. Unique Value of Studies of Biochemical Effector Systems.- References.- Section 4: Correlation of Binding Sites with Function.- 7 Autoreceptors Regulating Serotonin Release.- 1. Introduction.- 2. Historical Perspective.- 3. Methodological Considerations.- 3.1. In Vitro Identification of the 5-HT Autoreceptor.- 3.2. In Vivo Identification of the 5-HT Autoreceptor.- 4. 5-HT Autoreceptor Location.- 5. Drugs Active at the Terminal 5-HT Autoreceptor.- 5.1. Agonists.- 5.2. Antagonists.- 6. Interactions between the 5-HT Autoreceptor and Uptake Site.- 7. Relationship of the Terminal 5-HT Autoreceptor to Radioligand Binding Sites.- 8. Evidence for a Functional Role for 5-HT Autoreceptors.- 9. Therapeutic Possibilities for 5-HT Autoreceptor Agonists and Antagonists.- 10. Future Directions.- References.- 8 Electrophysiology of Central Serotonin Receptor Subtypes.- 1. Introduction.- 2. Physiology of 5-HT1 Receptors.- 2.1. Dorsal Raphé Nucleus.- 2.2. Hippocampal Pyramidal Cell Layer.- 3. Physiology of 5-HT2 Receptors.- 3.1. Facial Motor Nucleus.- 3.2. Prefrontal Cortex.- 3.3. Locus Ceruleus.- 4. Summary and Conclusions.- References.- 9 Behavioral Models of Serotonin Receptor Activation.- 1. Introduction.- 2. Conditioned Behavior Models.- 2.1. Schedule-Controlled Responding.- 2.2. Conflict Behavior.- 2.3. Drug Discrimination.- 3. Unconditioned Behavior Models.- 3.1. Serotonin Behavioral Syndrome.- 3.2. Head-Shaking Behavior.- 3.3. Locomotor Activity.- 3.4. Startle Response.- 3.5. Feeding Behavior.- 3.6. Temperature Regulation.- 3.7. Sexual Behavior.- 3.8. Aggressive Behavior.- 4. Summary.- References.- 10 Serotonin Receptors in Vascular Smooth Muscle.- 1. Introduction.- 2. Serotonin-Induced Vascular Contraction.- 2.1. Alpha-Adrenergic Receptor-Mediated Vascular Contraction.- 2.2. 5-HT2 Receptor-Mediated Vascular Contraction..- 2.3. Non-5-HT2 Receptor-Mediated Vascular Contraction.- 3. Serotonin-Induced Contractile Responses in Human Blood Vessels.- 4. Serotonin Receptor-Mediated Vascular Relaxation.- 5. Serotonergic Inhibitory Presynaptic Receptors on Nerves in Blood Vessels.- 6. 5-HT2 Receptor-Mediated Amplification of Vascular Contraction.- 7. 5-HT2 Receptor-Mediated Increases in Vascular Permeability.- 8. Serotonergic Activation of Second-Messenger Mechanisms.- 9. Summary.- References.- Section 5: Regulation of Serotonin Receptors.- 11 Regulation of Serotonin Receptors and Responsiveness in the Brain.- 1. Introduction.- 2. Receptors for 5-HT in the Central Nervous System.- 3. Regulation of Receptors for ACh, NE, and DA in the Central Nervous System.- 4. Supersensitivity to 5-HT in the Central Nervous System.- 4.1. Denervation-Induced Changes in Responsiveness.- 4.2. Denervation-Induced Changes in Serotonin Receptors.- 5. Serotonergic Responsiveness after Repeated Administration of Drugs That Acutely Enhance or Activate Serotonergic Transmission.- 5.1. …