Pfeilschifter J, Huwiler A, Merriweather C, Briner V A
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Eur J Pharmacol. 1992 Jan 14;225(1):57-62. doi: 10.1016/0922-4106(92)90039-x.
Angiotensin II stimulated a biphasic 1,2-diacylglycerol formation in [3H]arachidonic acid-labelled mesangial cells. In contrast, in cells labelled with [3H]myristic acid, a tracer that preferentially marks phosphatidylcholine, angiotensin II induced a delayed monophasic production of 1,2-diacylglycerol. This delayed peak of 1,2-diacylglycerol generation was associated with a concomitant increase in choline formation, suggesting that stimulation of mesangial cells with angiotensin II causes a phospholipase D-mediated phosphatidylcholine hydrolysis. This conclusion is supported by the observation that angiotensin II stimulated the accumulation of phosphatidylethanol, when ethanol was added to mesangial cells. The production of choline and phosphatidylethanol stimulated by angiotensin II was completely blocked by the angiotensin II AT1 receptor-selective antagonist DuP 753 with an IC50 value of 8 nM, but not by the angiotensin II AT2 receptor selective ligand CGP 42112A. Furthermore, angiotensin(1-7) and angiotensin(1-6) had only weak effects on choline generation. These data clearly indicate that angiotensin II AT1 receptors trigger phospholipase D-mediated phosphatidylcholine hydrolysis in rat mesangial cells.
血管紧张素II在[3H]花生四烯酸标记的系膜细胞中刺激了双相1,2 -二酰甘油的形成。相比之下，在用[3H]肉豆蔻酸标记的细胞中（[3H]肉豆蔻酸是一种优先标记磷脂酰胆碱的示踪剂），血管紧张素II诱导了1,2 -二酰甘油的延迟单相产生。这种1,2 -二酰甘油生成的延迟峰值与胆碱形成的同时增加相关，表明用血管紧张素II刺激系膜细胞会导致磷脂酶D介导的磷脂酰胆碱水解。当向系膜细胞中加入乙醇时，血管紧张素II刺激了磷脂酰乙醇的积累，这一观察结果支持了该结论。血管紧张素II刺激产生的胆碱和磷脂酰乙醇被血管紧张素II AT1受体选择性拮抗剂DuP 753完全阻断，IC50值为8 nM，但未被血管紧张素II AT2受体选择性配体CGP 42112A阻断。此外，血管紧张素(1 - 7)和血管紧张素(1 - 6)对胆碱生成的影响较弱。这些数据清楚地表明，血管紧张素II AT1受体在大鼠系膜细胞中触发磷脂酶D介导的磷脂酰胆碱水解。
