Pfeilschifter J, Kurtz A, Bauer C
Biochem J. 1986 Feb 15;234(1):125-30. doi: 10.1042/bj2340125.
It was the aim of the present study to find out if a common mechanism exists by which the vasoconstrictive hormones angiotension II, noradrenaline and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC) increase prostaglandin E2 (PGE2) synthesis in cultures of rat renal mesangial cells. Angiotension II, noradrenaline and AGEPC stimulated PGE2 synthesis and uptake of 45Ca2+ in cultured mesangial cells. Both of these effects could be completely suppressed by the calcium channel blocker verapamil. Angiotensin II, noradrenaline and AGEPC caused a rapid breakdown of phosphatidylinositol 4,5-bisphosphate with a concomitant increase of 1,2-diacylglycerol and inositol trisphosphate, indicating an activation of phospholipase C by these hormones. Addition of verapamil had no effect on the hormone-induced stimulation of phospholipase C. The synthetic analogue of diacylglycerol, 1-oleoyl-2-acetylglycerol, and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), both of which are known to stimulate protein kinase C, enhanced PGE2 synthesis. Chelation of extracellular calcium with EDTA or addition of verapamil abolished the effect of 1-oleoyl-2-acetylglycerol and phorbol ester on PGE2 synthesis. 1-Oleoyl-2-acetylglycerol and phorbol ester increased the uptake of 45Ca2+ by the cells in a dose-dependent manner and this effect could be blocked by verapamil. The entirety of these data leads us to suggest that vasoconstrictor-evoked synthesis of PGE2 in rat mesangial cells is mediated by the subsequent activation of phospholipase C and protein kinase C. The activation of protein kinase C by diacylglycerol is likely to be involved in the increase of the calcium permeability of the plasma membrane which is a prerequisite for PGE2 synthesis induced by vasoconstrictive hormones.
本研究的目的是确定血管收缩激素血管紧张素II、去甲肾上腺素和1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱（AGEPC）是否通过一种共同机制增加大鼠肾系膜细胞培养物中前列腺素E2（PGE2）的合成。血管紧张素II、去甲肾上腺素和AGEPC刺激培养的系膜细胞中PGE2的合成以及45Ca2+的摄取。这两种效应都可被钙通道阻滞剂维拉帕米完全抑制。血管紧张素II、去甲肾上腺素和AGEPC导致磷脂酰肌醇4,5-二磷酸迅速分解，同时1,2-二酰基甘油和肌醇三磷酸增加，表明这些激素激活了磷脂酶C。添加维拉帕米对激素诱导的磷脂酶C刺激没有影响。二酰基甘油的合成类似物1-油酰基-2-乙酰基甘油和佛波酯12-O-十四烷酰佛波醇13-乙酸酯（TPA），两者都已知可刺激蛋白激酶C，增强了PGE2的合成。用EDTA螯合细胞外钙或添加维拉帕米消除了1-油酰基-2-乙酰基甘油和佛波酯对PGE2合成的影响。1-油酰基-2-乙酰基甘油和佛波酯以剂量依赖的方式增加细胞对45Ca2+的摄取，且这种效应可被维拉帕米阻断。所有这些数据使我们认为，大鼠系膜细胞中血管收缩剂诱发的PGE2合成是由随后磷脂酶C和蛋白激酶C的激活介导的。二酰基甘油对蛋白激酶C的激活可能参与了质膜钙通透性的增加，这是血管收缩激素诱导PGE2合成的先决条件。
