Sterin-Speziale N B, Setton C P, Kahane V L, Speziale E H
Department of Biological Chemistry, Buenos Aires University, Argentina.
Biochem Pharmacol. 1989 Mar 1;38(5):725-8. doi: 10.1016/0006-2952(89)90224-4.
In view of the fact that mepacrine (Mp) is usually used as an inhibitor of the endogenous phospholipase A2, and since this enzyme produces the release of arachidonic acid (AA) from membrane phospholipids, we studied the effect of different concentrations of Mp on the mobilization of [1-14C]AA in rat renomedullary phospholipids. During the acylation period, 0.1 mM Mp did not produce any significant change in the incorporation of [1-14C]AA into phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and only a slight increase in phosphatidylinositol (PI). Higher concentrations of Mp (0.5 to 1.0 mM) produced a decrease of radioactivity in PE and PC with an increase in PI. Using prelabeled slices, a dose-dependent decrease in the 14C-radioactivity in PE and PC was observed, with a parallel increase in PI. This effect of Mp persisted even in the presence of a physiological activator of phospholipase A2, bradykinin (BK). No change in the net amount of phospholipids was observed at any of the Mp concentrations used. The results of this study show that Mp, at concentrations generally used to inhibit phospholipase A2, produced a transfer of arachidonic acid from PE and PC to PI, rather than a blockade in the release of AA from membrane phospholipids.
鉴于阿的平（Mp）通常用作内源性磷脂酶A2的抑制剂，且该酶可促使花生四烯酸（AA）从膜磷脂中释放出来，我们研究了不同浓度的Mp对大鼠肾髓质磷脂中[1-14C]AA动员的影响。在酰化期间，0.1 mM的Mp对[1-14C]AA掺入磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）没有产生任何显著变化，仅使磷脂酰肌醇（PI）略有增加。较高浓度的Mp（0.5至1.0 mM）使PE和PC中的放射性降低，而PI增加。使用预先标记的切片，观察到PE和PC中14C放射性呈剂量依赖性降低，同时PI平行增加。即使在磷脂酶A2的生理激活剂缓激肽（BK）存在的情况下，Mp的这种作用仍然持续。在所使用的任何Mp浓度下，均未观察到磷脂总量的变化。本研究结果表明，通常用于抑制磷脂酶A2的浓度的Mp会使花生四烯酸从PE和PC转移至PI，而不是阻断AA从膜磷脂中的释放。
