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 re ceptor antagonist, on platelet aggregation was examined as well as the rela tionship to serotonin and P-selectin, a platelet alpha-granule membrane gly coprotein. platelet aggregation was induced by simultaneous addition of col lagen (0.06-0.12 mu g/ml), which did not induce aggregation alone, and sero tonin (0.88 mu mol/l) to platelet-rich plasma (PRP). The PRP was obtained f rom healthy volunteers and percentage maximum aggregation (MA) was measured . Serotonin levels and P-selectin levels in the supernatant of PRP after ag gregation were determined. When vehicle-treated PRP was stimulated in the a forementioned manner, platelet aggregation dependent on collagen concentrat ion was induced. Serotonin levels and P-selectin levels were also dependent on collagen concentration. Sarpogrelate (10(-6) to 10(-4) mol/l) inhibited such aggregation dose-dependently, and decreased serotonin levels and P-se lectin levels in a dose-dependent manner. There were close correlations bet ween MA and serotonin levels, MA and P-selectin levels, as well as serotoni n and P-selectin levels. These results suggest that extracellular release o f serotonin and P-selectin from platelets was caused by induction of aggreg ation, and these responses were suppressed by sarpogrelate. (C) 1999 Lippin cott Williams & Wilkins.