Binding characteristics of [3H]ketanserin for serotonin-2 receptor in the rabbit platelet

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-1. 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 alpha-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-1, were 7.19 and 7.59, respectively and these values were lower than those of ketanserin and pirenperone but higher than those of methysergide, cinanserin 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-1 had the same affinities to the receptors in the rat frontal lobe and in the rabbit platelet.(ABSTRACT TRUNCATED AT 250 WORDS)