Problems in in vitro receptor binding studies and identification and role of serotonin receptor sites.

The principles and problems in neurotransmitter receptor radioligand binding studies are discussed. Various types of ligand-membrane interactions are described and criteria and ways for identification of specific receptor binding sites are evaluated. It is questioned whether the endogenous neurotransmitters must have binding affinities of nanomolar order for their receptor sites. The relationship between the numbers of receptor binding sites and functional activity of the receptors is investigated. Serotonin-S1 binding sites are sites labelled at nanomolar concentrations by [3H]serotonin. Various alleged roles for these sites are considered and found to be insufficiently substantiated. Therefore these sites should not yet be regarded as receptor sites. Serotonin-S2 binding sites are sites labelled by potent serotonin antagonists. The sites show a typical distribution in the mammalian brain and are present on blood platelets. The neuronal localization of the sites, investigated by lesion studies is discussed. Serotonin-S2 sites have a role in serotonin-induced behavioural excitation in laboratory animals. A presumed role for the sites in depression and anxiety is to be investigated. Serotonin-S2 sites were also shown to mediate serotonin-induced vasoconstriction and platelet aggregation. The sites were hypothesized from pharmacological and electrophysiological studies. Appropriate tools are lacking for a clear characterization of the multiple sites.