Kojima I, Kojima K, Rasmussen H
Endocrinology. 1985 Sep;117(3):1057-66. doi: 10.1210/endo-117-3-1057.
When [3H]arachidonic acid-labeled calf adrenal glomerulosa cells are stimulated by angiotensin II (AII), free [3H]arachidonic acid is released. AII treatment significantly decreases radioactivity in phosphatidylinositol but not in other phospholipids. Inhibitors of phospholipase A2 (PL-A2) activity, quinacrine and p-bromophenacyl bromide, inhibit AII-stimulated aldosterone secretion from glomerulosa cells in a dose-dependent manner. The effect of these inhibitors is irreversible when used at high concentration, but not when employed at lower concentration. Exogenous PL-A2 as well as arachidonic acid stimulates both radiocalcium efflux and aldosterone secretion. Unlike AII, stimulation of aldosterone secretion by PL-A2 is only transient. Radiocalcium efflux induced by PL-A2 is greater than that induced by AII and is not inhibited by either nitrendipine or dantrolene. Pretreatment with PL-A2 abolishes the radiocalcium efflux response to subsequent AII, whereas AII pretreatment does not abolish the subsequent PL-A2-mediated radiocalcium efflux response. The aldosterone secretory response to AII is not affected by 0.3 microM indomethacin but is inhibited by either of three compounds which inhibit lipoxygenase activity; 5,8,11,14-eicosatetraynoic acid, BW755c, or caffeic acid. In a static incubation system, AII-stimulated aldosterone secretion is inhibited 40-50% by any of these lipoxygenase inhibitors. In a perifusion system, BW755c partially inhibits only the sustained phase of AII-stimulated aldosterone secretion. However, BW755c has no effect on the secretion of aldosterone in response to combined A23187 plus 12-O-tetradecanoyl-phorbol-13-acetate. These results suggest that PL-A2 action is not obligatory in AII-induced aldosterone secretion and that lipoxygenase, but not cyclooxygenase, products of arachidonic acid metabolism may play a role in AII action as positive feed forward mediators.
当用[3H]花生四烯酸标记的小牛肾上腺球状带细胞受到血管紧张素II（AII）刺激时，游离的[3H]花生四烯酸会被释放出来。AII处理可显著降低磷脂酰肌醇中的放射性，但对其他磷脂无此作用。磷脂酶A2（PL - A2）活性抑制剂奎纳克林和对溴苯甲酰溴以剂量依赖的方式抑制球状带细胞中AII刺激的醛固酮分泌。这些抑制剂在高浓度使用时其作用是不可逆的，但在低浓度使用时则不是。外源性PL - A2以及花生四烯酸均可刺激放射性钙外流和醛固酮分泌。与AII不同，PL - A2刺激醛固酮分泌只是短暂的。PL - A2诱导的放射性钙外流大于AII诱导的，且不受尼群地平或丹曲林的抑制。用PL - A2预处理可消除随后对AII的放射性钙外流反应，而AII预处理则不会消除随后PL - A2介导的放射性钙外流反应。对AII的醛固酮分泌反应不受0.3微摩尔吲哚美辛的影响，但受到三种抑制脂氧合酶活性的化合物中的任何一种的抑制；5,8,11,14 - 二十碳四炔酸、BW755c或咖啡酸。在静态孵育系统中，这些脂氧合酶抑制剂中的任何一种均可使AII刺激的醛固酮分泌受到40 - 50%的抑制。在灌流系统中，BW755c仅部分抑制AII刺激的醛固酮分泌的持续阶段。然而，BW755c对A23187加12 - O - 十四酰佛波醇 - 13 - 乙酸酯联合刺激引起的醛固酮分泌无影响。这些结果表明，PL - A2的作用在AII诱导的醛固酮分泌中并非必需，并且花生四烯酸代谢的脂氧合酶产物而非环氧化酶产物可能作为正反馈前馈介质在AII作用中发挥作用。
