Key result
In calf adrenal glomerulosa cells, phospholipase A2 action is not obligatory for angiotensin II-induced aldosterone secretion, whereas lipoxygenase products may act as positive feed-forward mediators.
This preclinical study suggests that lipoxygenase products of arachidonic acid metabolism, rather than phospholipase A2 action, play a role as positive feed-forward mediators in angiotensin II-induced aldosterone secretion.
Preclinical calf-cell data should not change clinical aldosterone management; leaves open lipoxygenase products as feed-forward mediators in angiotensin II signaling.
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.
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Kojima et al. (1985) studied this question. Angiotensin II, Phospholipase A2 inhibitors, and lipoxygenase inhibitors was evaluated on Aldosterone secretion and radiocalcium efflux. In calf adrenal glomerulosa cells, phospholipase A2 action is not obligatory for angiotensin II-induced aldosterone secretion, whereas lipoxygenase products may act as positive feed-forward mediators.
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