Binding Characteristics of [3H]Ketanserin for Serotonin-2 Receptor in the Rabbit Platelet

Abstract

The present study was designed to examine 1) the properties of [3H]ketanserin binding to serotonin-2 (5HT2)-serotonergic receptors in the rabbit platelet membranes, 2) displacement affinities of various chemicals and 3) difference of the affinities between their chemicals and new agents, MCI-9042 and M-l. The plots of specific binding obtained from the Scatchard analysis using [3H]ketanserin for the platelet membranes were monophasic when the non-specific binding was determined by the use of 0.1 mM serotonin (5HT), and the Kd and Bmax values were 3.93 ±0.41 nM and 1.19 ± 0.20 pmol/mg protein, respectively. The displacement potencies of chemicals which were serotonin receptor-, dopamine receptor-, histamine receptor-, and α-adrenoceptor-related agents were characterized by [3H]ketanserin binding to 5HT2-serotonergic receptor. The pKi values of a new antiplatelet agent, MCI-9042, and its metabolite, M-l, were 7.19 and 7.59, respectively and these values were lower than those of ketanserin and pirenperone but higher than those of methysergide, cinanse-rin and cyproheptadine. The affinities of ketanserin for 5HT2-receptors in the rabbit platelet were similar to those for 5HT2-receptors previously identified in the rat frontal lobe and in canine aorta, but cinancerin was selective to 5HT2-receptors in the rat frontal lobe and in canine aorta, prazosin was selective to 5HT2-receptor in the rabbit platelet, and MCI-9042 and M-l had the same affinities to the receptors in the rat frontal lobe and in the rabbit platelet. It is suggested that 1) the binding of [3H]ketanserin to 5HT2-receptors in the rabbit platelet is dissociated by the new antiplatelet agents, MCI-9042 and M-l, 2) the affinities of some chemicals for 5HT2-receptors in the rabbit platelet are not identical with those in the rat frontal lobe or in the canine aorta, and 3) [3H]ketanserin binding sites in platelets, neurons and/or blood vessels may consist of various subtypes. © 1991, The Pharmaceutical Society of Japan. All rights reserved.