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

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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)

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