Possible Role of Phospholipase A2Action and Arachidonic Acid Metabolism in Angiotensin II–Mediated Aldosterone Secretion*

Abstract

When [³H]arachidonic acid-labeled calf adrenal glomerulosa cells are stimulated by angiotensin II (All), free [³H]arachidonic acid is released. All treatment significantly decreases radioactivity in phosphatidylinositol but not in other phospholipids. Inhibitors of phospholipase A₂ (PL–A₂) activity, quinacrine and p–bromophenacyl bromide, inhibit All–stimulated aldosterone secretion from glomerulosa cells in a dosedependent 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 All, stimulation of aldosterone secretion by PL–A₂ is only transient. Radiocalcium efflux induced by PL–A₂ is greater than that induced by All and is not inhibited by either nitrendipine or dantrolene. Pretreatment with PL–A₂ abolishes the radiocalcium efflux response to subsequent All, whereas All pretreatment does not abolish the subsequent PL–A₂–mediated radiocalcium efflux response. The aldosterone secretory response to All is not affected by 0.3 μM 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, All–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 All–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 All–induced aldosterone secretion and that lipoxygenase, but not cyclooxygenase, products of arachidonic acid metabolism may play a role in All action as positive feed forward mediators. (Endocrinology117: 1057–1066, 1985)