Effects of sarpogrelate hydrochloride on platelet aggregation, and its relation to the release of serotonin and P-selectin

Inhibitory effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 receptor antagonist, on platelet aggregation was examined as well as the relationship to serotonin and P-selectin, a platelet alpha-granule membrane glycoprotein. Platelet aggregation was induced by simultaneous addition of collagen (0.06–0.12 μg/ml), which did not induce aggregation alone, and serotonin (0.88 μmol/l) to platelet-rich plasma (PRP). The PRP was obtained from healthy volunteers and percentage maximum aggregation (MA) was measured. Serotonin levels and P-selectin levels in the supernatant of PRP after aggregation were determined. When vehicle-treated PRP was stimulated in the aforementioned manner, platelet aggregation dependent on collagen concentration was induced. Serotonin levels and P-selectin levels were also dependent on collagen concentration. Sarpogrelate (10 to 10 mol/1) inhibited such aggregation dose-dependently, and decreased serotonin levels and P-selectin levels in a dose-dependent manner. There were close correlations between MA and serotonin levels, MA and P-selectin levels, as well as serotonin and P-selectin levels. These results suggest that extracellular release of serotonin and P-selectin from platelets was caused by induction of aggregation, and these responses were suppressed by sarpogrelate. Blood Coag Fibrinol 10:513–519 © 1999 Lippincott Williams & Wilkins.