Fukunaga M, Fujiwara Y, Ochi S, Yokoyama K, Shoji T, Fukuhara Y, Orita Y, Kamada T, Badr K F, Ueda N
Department of Medicine, Emory University, Decatur, GA 30033, USA.
Exp Nephrol. 1996 Nov-Dec;4(6):340-9.
The phospholipase A2 inhibitors mepacrine, ONO-RS-082, and AACOCF3 completely inhibited prostaglandin E2 production induced by endothelin 1 in cultured rat mesangial cells, suggesting that phospholipase A2 is a critical enzyme in this process. TMB-8, an inhibitor of calcium mobilization from intracellular stores, abolished its production, while neither nicardipine nor chelation of extracellular calcium by EGTA did. The protein kinase C inhibitors, H-7 and staurosporine, and downregulation of protein kinase C could not inhibit prostaglandin E2 production, while W-7, a calmodulin inhibitor, abolished it. Pertussis toxin never influenced its production. Thus, endothelin 1 evokes prostaglandin E2 production in mesangial cells mainly through the activation of phospholipase A2, dependent on intracellular calcium and calmodulin and independent of extracellular calcium, protein kinase C, and pertussis toxin sensitive guanosine 5'-triphosphate binding proteins.
磷脂酶A2抑制剂米帕林、ONO-RS-082和AACOCF3完全抑制了内皮素1在培养的大鼠系膜细胞中诱导的前列腺素E2生成，这表明磷脂酶A2在此过程中是一种关键酶。TMB-8是一种细胞内钙库钙动员的抑制剂，它消除了前列腺素E2的生成，而尼卡地平或EGTA对细胞外钙的螯合作用均未产生此效果。蛋白激酶C抑制剂H-7和星形孢菌素以及蛋白激酶C的下调均不能抑制前列腺素E2的生成，而钙调蛋白抑制剂W-7则消除了其生成。百日咳毒素从未影响其生成。因此，内皮素1主要通过激活磷脂酶A2在系膜细胞中诱发前列腺素E2生成，这一过程依赖于细胞内钙和钙调蛋白，而与细胞外钙、蛋白激酶C以及百日咳毒素敏感的鸟苷5'-三磷酸结合蛋白无关。
