Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells.
We investigated the effects of the new 5-HT2A receptor antagonist, sarpogrelate, on DNA synthesis in renal mesangial cells stimulated with 5-HT in the presence and absence of platelet-derived growth factor (PDGF)-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-dependent manner. In the presence of PDGF-BB, sarpogrelate had a weaker anti-mitogenic 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 glomerulonephritis associated with mesangial cell proliferation.
Eto
Y
Y
Department of Medicine, Tokyo Women's Medical College, Japan.
Nitta
K
K
Uchida
K
K
Tsutsui
T
T
Natori
K
K
Kawashima
A
A
Yumura
W
W
Nihei
H
H
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013386:Succinates / Q000494:pharmacology*
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin; D004247:DNA; D007770:L-Lactate Dehydrogenase