Chapter 1. Biochemical Models for Serotonin Receptors

Abstract

Publisher Summary This chapter discusses the specificity of ligands used for the characterization of these sites, the distribution of the sites in the brain tissue, the activities of a variety of pharmaca at the sites and correlations with in vitro and in vivo pharmacological activities, some structure–activity relationships, the in vivo regulation of the sites, and their hypothesized involvement in human diseases. The specificity of the ligands and occurrence of the serotonin receptor sites—the enzyme activity of serotonin-stimulated adenylate cyclase—is best detectable in Colliculli of young animals, because the activity is found to decrease rapidly with age. The enzyme was reported to be present in glial cell preparations from horse brain striatumand in a particulate fraction of the central nervous system (CNS) of the snail Helix Pomatia . The S 1 binding sites are labeled with affinity by 3H-serotonin. For specific binding of the 3 H-serotonin, defined by inhibition with 10 μIM unlabelled serotonin assayed at 37 o C, K D -values of 1.4nM14 to 8nM are reported. The labeling of S 2 -receptor binding sites are discussed in this chapter. The binding affinity of drugs for the putative serotonin receptor sites and relationship with pharmacological activity has been explained in the chapter. The S 1 -binding sites and the serotonin-stimulated adenylate dyclase being unrelated a supposed coupling between the two systems was refuted. S 1 -binding data indicates that the sites are to be considered as mere binding sites until further proof for a receptor function is furnished. Correlation between the activities of compounds in biochemical models and in pharmacological models for serotonin receptors S 2 -receptor-binding sites mediate various actions of serotonin and that the binding affinities of serotonin, serotonin-like compounds, and serotonin antagonists are completely compatible with the anticipated features of a serotonin neurotransmitter receptor. A description of the structure–activity relationships at the S 2 -receptor-binding sites and a role for S 2 -receptor alterations in several disease states has been discussed in the chapter.