ANTI-MITOGENIC EFFECTS OF SARPOGRELATE IN CULTURED RAT MESANGIAL CELLS

We investigated the effects of the new 5-HT2A receptor antagonist, sar pogrelate, on DNA synthesis in renal mesangial cells stimulated with 5 -HT in the presence and absence of platelet-derived growth factor (PDG F)-BB. Both 5-HT and PDGF-BB demonstrated a mitogenic effect on these cells. When mesangial cells were incubated in the absence of PDGF-BB, sarpogrelate inhibited DNA synthesis in these cells in a dose-dependen t manner. In the presence of PDGF-BB, sarpogrelate had a weaker anti-m itogenic effect in mesangial cells stimulated with 5-HT. Sarpogrelate was cytotoxic at concentrations over 10(-5) M according to the results of LDH release assays, and it reduced the S1 phase in mesangial cells stimulated with 5-HT by a flow cytometry. These findings suggest that sarpogrelate may be effective in the treatment of some glomerulonephr itis associated with mesangial cell proliferation.