Characteristics of agonist displacement of [³H]ketanserin binding to platelet 5-HT(2A) receptors: Implications for psychiatric research

Brain 5-HT(2A) 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 [³H]ketanserin's saturable binding to platelet 5- HT(2A) receptors and characteristics of agonist displacement curves of [³H]ketanserin binding in healthy control subjects. [³H]ketanserin saturation curves showed a trend for a two-site model, reflecting two independent binding sites. At low [³H]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-HT(2A) receptors exist in two agonist affinity states that are regulated by G(q) protein. Platelet 5- HT(2A) 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.