Serotoninergic receptors in brain tissue: properties and identification of various 3H-ligand binding sites in vitro.

In vitro binding studies to serotoninergic receptors were performed using 3H-LSD, 3H-5-HT and 3H-spiperone. An overview is given on findings using these three ligands with respect to the following: (1) Localization of specific binding sites, i.e., in various animal species, the regional distribution in the brain and periphery, the subcellular and cellular distribution. (2) Properties of the binding sites, i.e., influence of the composition of the assay medium, binding kinetic properties, receptor regulation in vivo. (3) Identity of the binding sites, i.e., differences between sites for various 3H-ligands, pharmacological specificity of the membranous binding sites, chemical composition of the macromolecular complex constituting the binding site. (4) Function of the receptor. Binding affinities of 44 compounds were measured in binding assays using 3H-spiperone and 3H-LSD with rat frontal cortex membrane preparations and using 3H-5-HT and 3H-LSD with rat hippocampal membrane preparations. A significant correlation between binding affinities for 3H-LSD and 3H-spiperone binding sites in the frontal cortex was found. Binding to these sites correlates with potencies of compounds to antagonize 5-HT-induced contraction in isolated rat caudal arteries and also with potencies of compounds to antagonize tryptamine-induced clonic seizures in rats. There was a very significant correlation between binding affinities for 3H-LSD and 3H-5-HT labelled sites in the hippocampus. These hippocampal binding sites are different from those for 3H-LSD and 3H-spiperone in the frontal cortex. Binding to 3H-5-HT or 3H-LSD sites in the hippocampus could not be related to a pharmacological effect.