Characteristics of agonist displacement of [3H]ketanserin binding to platelet 5-HT2A receptors:: implications for psychiatric research

Brain 5-HT2A receptors exist in two agonist affinity states as a function of their coupling to G(q) protein. This has not yet been shown in platelets. We examined [H-3]ketanserin's saturable binding to platelet 5-HT2A receptors and characteristics of agonist displacement curves of [H-3]ketanserin binding in healthy control subjects. [H-3]ketanserin saturation curves showed a trend for a two-site model, reflecting two independent binding sites. At low [H-3]ketanserin concentrations, agonist displacement curves were flat and best fit a two-site model, indicating the existence of two agonist affinity states. Guanylyl 5'-imidotriphosphate [Gpp(NH)p] induced a significant rightward shift in agonist displacement curves to fit a one-site model. Platelet membrane 5-HT2A receptors exist in two agonist affinity states that are regulated by G(q) protein. Platelet 5-HT2A receptors provide an accessible model for examining possible dysregulation in the agonist affinity or coupling efficiency to the phosphoinositide system in psychiatric disorders and their modulation by psychotropic medications. Published by Elsevier Science Ireland Ltd.