Possible role of phospholipase A2 action and arachidonic acid metabolism in angiotensin II-mediated aldosterone secretion.

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.