Effects of sarpogrelate on serotonin-induced increases in cytosolic Ca2+ in cultured rat mesangial cells.

The effects of the new 5-HT2A receptor antagonist sarpogrelate on the cellular action of serotonin were examined in cultured rat mesangial cells by measuring cytosolic free calcium concentration ([Ca2+]i). Sarpogrelate inhibited serotonin-induced increases in [Ca2+]i in a concentration-dependent manner. M1, a major metabolite of sarpogrelate, also exhibited an inhibitory effect exceeding that of sarpogrelate. The inhibitory effects of sarpogrelate and M1 were abolished by washing out these compounds. In contrast, the increase in [Ca2+]i induced by angiotensin II or arginine vasopressin was not affected by pretreatment of the cells with sarpogrelate or M1. These results suggest that sarpogrelate and its major metabolite (M1) act as reversible and specific 5-HT2A receptor antagonists against the contractile action of platelet-derived serotonin in mesangial cells.