Serotonin-S 2 receptor binding sites and functional correlates

Abstract

Serotonin-S 2 receptor binding sites have been labelled with several ligands such as [ 3H]spiperone, [ 3H]lysergic acid diethylamide (LSD), [ 3H]mianserin and [ 3H]ketanserin, the latter being the most selective ligand. The greatest concentration of the sites occurs in frontal cortical tissue, but they were also detected in striatum, nucleus accumbens and tuberculum olfactorium as well as on membranes of cat and human platelets. The serotonin-S 2 sites, labelled with different ligands in different tissues, revealed similar binding properties for drugs, but careful definition of specific binding is necessary because of marked variation in the non-specific binding of drugs in different tissues. Serotonin-S 2 sites were demonstrated to have a role in serotonin-induced behavioural excitation in rodents and they probably mediate perception of subjective feelings elicited by serotonin mimetics. In vivo studies revealed involvement of the serotonin-S 2 sites in impairment of microcirculation by serotonin and in inflammation provoked by serotonin. On isolated tissues, serotonin-S 2 sites mediate serotonin-induced vasoconstriction in peripheral blood vessels (e.g. superficial, coronary, splanchnic vessels) and cerebral blood vessels from various species including man. Serotonin-S 2 sites also have a role in serotonin-induced contractions in tracheal smooth muscle and serotonin-induced bronchoconstriction in vivo, but the sites are unrelated to “M”- and “D”-serotonin receptor subtypes, which have been functionally characterized in gastrointestinal smooth muscle. Platelets proved to be an integral model for studying serotonin-S 2 sites. Binding, measured on platelet membranes, was shown to be directly related to serotonin-induced platelet aggregation or changes in shape. Evidence was obtained that inositol-lipid turnover is a primary response following stimulation of serotonin-S 2 receptors in platelets. It is likely to be part of the signal-transducing system in which calcium is a second messenger candidate. Platelets are a promising tool for the study of alterations in serotonin-S 2 receptors in disease states and after treatment with drugs.