Prostaglandin E2-induced aldosterone release is mediated by an EP2 receptor

Prostaglandin E-2 (PGE(2)) is an endogenous hormone of adrenal zona glomerulosa cells and is released in response to stimulation by agonists such as angiotensin II (Ang II). It stimulates the release or aldosterone from cultured bovine adrenal zona glomerulosa cells, These studies were designed to determine whether this steroidogenic effect of PGE, was mediated by an EP1, EP2, or EP3 receptor. Prostaglandin E-2 and 11-deoxy PGE(1), an EP2-selective agonist, stimulated aldosterone release in a concentration-related manner with an ED50 of 300 nmol/L for PGE(2) and 2 mu mol/L for 11-deoxy PGE(1). The maximal effect of PGE(2) was less than that of angiotensin II. 17-Phenyl trinor PGE(2), an EP1-selective agonist, required concentrations of 100 nmol/L to stimulate aldosterone release and sulprostone, an EP3/EP1-selective agonist, railed to alter aldosterone release. The EP1-selective antagonist SC19220 failed to alter basal or PGE(2)-stimulated aldosterone release over-a range of concentrations. PGE(2) and 11-deoxy PGE(1) also stimulated an increase in both intracellular and extracellular cAMP. This increase was time-and concentration-related. The ED50 for PGE(2) was 9.8 mu mol/L. 17-Phenyl trinor PGE(2) and sulprostone were without effect. Using fura-2 loaded cells, PGE(2) (2 mu mol/L), dibutyryl cAMP (2 mmol/L), and Ang II (2 mu mol/L) increased intracellular calcium over basal concentrations by 5.5-fold, 3-fold, and 6.2-fold, respectively. Like PGE(2), dibutyryl cAMP also stimulated aldosterone release. PGE(2-) and dibutyryl cAMP-induced aldosterone release were blocked by the calcium channel inhibitor diltiazem. These studies indicate that PGE(2) is a potent stimulus for aldosterone release and that the effects is mediated by EP2 receptors. Both cAMP and calcium appear to mediate the steroidogenic effect of PGE(2) and calcium seems to be distal to cAMP.