Phorbol ester inhibits arginine vasopressin activation of phospholipase C and promotes contraction of, and prostaglandin production by, cultured mesangial cells.
Phorbol ester inhibits arginine vasopressin activation of phospholipase C and promotes contraction of, and prostaglandin production by, cultured mesangial cells.
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佛波酯抑制磷脂酶 C 的精氨酸加压素活化，并促进培养的肾小球系膜细胞的收缩和前列腺素的产生。
DOI：
10.1042/bj2510907
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Kreisberg,JI
中科院分区：
文献类型：
--
作者：
Troyer,DA;Gonzalez,OF;Douglas,JG;Kreisberg,JI
我们之前已经证明，精氨酸加压素（AVP）会在涂在光滑基质（例如聚（甲基丙烯酸羟乙酯）包被的培养皿）上的培养的系膜细胞中引起快速（5-10 分钟）收缩反应。这种收缩与肌醇三磷酸 (InsP3)、二酰甘油和前列腺素 E2 (PGE2) 水平的增加有关。我们现在报道已知可激活蛋白激酶 C 的药物，即佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 和油酰乙酰甘油 (OAG)，也能收缩系膜细胞；然而，收缩反应发展缓慢（15-30 分钟）。无活性的佛波酯，4α-佛波醇12,13-二癸酸酯，不引起收缩。 PMA 和 OAG 不会增加系膜细胞中 InsP3 的释放。然而，用PMA预处理系膜细胞抑制了InsP3的形成。这种抑制不能用 AVP 结合的减少来解释，因为 PMA 处理不影响完整细胞中 [3H]AVP 结合位点的数量或亲和力。 PMA 单独刺激系膜细胞中 PGE2 的产生，其程度与 AVP 相似。与 InsP3 所观察到的相反，在 AVP 之前用 PMA 预处理细胞对花生四烯酸的释放和 PGE2 的产生具有累加效应。因此，磷脂酶 C 的活性与磷脂酶 A2 的活性明显分离。
We have previously shown that arginine vasopressin (AVP) causes a rapid (5-10 min) contractile response in cultured mesangial cells plated onto slippery substrata such as poly(hydroxyethyl methacrylate)-coated dishes. This contraction is associated with an increase in the levels of inositol trisphosphate (InsP3), diacylglycerol and prostaglandin E2 (PGE2). We now report that agents which are known to activate protein kinase C, i.e. phorbol 12-myristate 13-acetate (PMA) and oleolylacetylglycerol (OAG), also contract mesangial cells; however, the contractile response is slow to develop (15-30 min). The inactive phorbol ester, 4 alpha -phorbol 12,13-didecanoate, did not elicit contraction. PMA and OAG did not increase InsP3 release in mesangial cells. However, pretreatment of mesangial cells with PMA inhibited the formation of InsP3. This inhibition could not be explained by a reduction in AVP binding since PMA treatment did not influence the number or affinity of [3H]AVP binding sites in intact cells. PMA alone stimulated PGE2 production in mesangial cells to a degree similar to AVP. Contrary to what was seen with InsP3, pretreatment of cells with PMA before AVP had an additive effect on arachidonic acid release and PGE2 production. Thus, there is an apparent dissociation of phospholipase C activity from that of phospholipase A2.