CHARACTERISTICS OF AGONIST DISPLACEMENT OF [H-3]KETANSERIN BINDING TOPLATELET 5-HT2A RECEPTORS - IMPLICATIONS FOR PSYCHIATRIC RESEARCH

Brain 5-HT2A receptors exist in two agonist affinity states as a funct ion 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 o f [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, ago nist displacement curves were flat and best fit a two-site model, indi cating the existence of two agonist affinity states. Guanylyl 5'-imido triphosphate [Gpp(NH)p] induced a significant rightward shift in agoni st displacement curves to fit a one-site model. Platelet membrane 5-HT 2A receptors exist in two agonist affinity states that are regulated b y G(q) protein. Platelet 5-HT2A receptors provide an accessible model for examining possible dysregulation in the agonist affinity or coupli ng efficiency to the phosphoinositide system in psychiatric disorders and their modulation by psychotropic medications. Published by Elsevie r Science Ireland Ltd.