In vitro steroidogenic properties of FK 33 824, a stable analog of methionine-enkephalin. Opiate-dopamine interaction in the control of aldosterone production

The steroidogenic properties of a stable analog of the endogenous opioid methionine-enkephalin, FK 33 824, were studied with calf adrenal glomerulosa cells and its effects were compared to those of angiotensin II (A II) and metoclopramide. Metoclopramide, A II, and FK 33 824 induced dose-related increases in aldosterone production. The order of potency in stimulating aldosterone was A II, FK 33 824, metoclopramide. Metoclopramide and FK 33 824 did not increase cortisol production. The response to A II but not to FK 33 824 was inhibited by equimolar concentrations of (Sar1 Ala8) antagonist analog of AII (saralasin acetate). By contrast in the presence of equimolar concentrations of naloxone, an opioid receptor antagonist, FK 33 824-induced aldosterone production was markedly inhibited while the response to A II was unchanged. Increases in cAMP accompanied the steroidogenic response to ACTH but not to A II or FK 33 824. Dopamine at physiological concentrations (10(-10) M) inhibited FK 33 824-induced aldosterone production. These results suggest that FK 33 824 is an aldosterone secretagogue and that it initiates steroidogenesis by mechanisms similar to those of A II. However the inability to block its effect with a specific antagonist of A II provides evidence for its action on a separate site.