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(Hypertension. 1998;31:575-581.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Prostaglandin E₂–Induced Aldosterone Release Is Mediated by an EP₂ Receptor

Stephen Csukas; Craig J. Hanke; David Rewolinski; ; William B. Campbell

From the Medical College of Wisconsin, Departments of Ophthalmology and Pharmacology and Toxicology, Milwaukee, Wis.

Correspondence to William B. Campbell, PhD, Medical College of Wisconsin, Department of Pharmacology and Toxicology, 8701 Watertown Plank Rd, Milwaukee, WI 53226-0509.

Abstract—Prostaglandin E₂ (PGE₂) 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 of aldosterone from cultured bovine adrenal zona glomerulosa cells. These studies were designed to determine whether this steroidogenic effect of PGE₂ was mediated by an EP₁, EP₂, or EP₃ receptor. Prostaglandin E₂ and 11-deoxy PGE₁, an EP₂-selective agonist, stimulated aldosterone release in a concentration-related manner with an ED₅₀ of 300 nmol/L for PGE₂ and 2 µmol/L for 11-deoxy PGE₁. The maximal effect of PGE₂ was less than that of angiotensin II. 17-Phenyl trinor PGE₂, an EP₁-selective agonist, required concentrations of 100 µmol/L to stimulate aldosterone release and sulprostone, an EP₃/EP₁-selective agonist, failed to alter aldosterone release. The EP₁-selective antagonist SC19220 failed to alter basal or PGE₂-stimulated aldosterone release over a range of concentrations. PGE₂ and 11-deoxy PGE₁ also stimulated an increase in both intracellular and extracellular cAMP. This increase was time- and concentration-related. The ED₅₀ for PGE₂ was 9.8 µmol/L. 17-Phenyl trinor PGE₂ and sulprostone were without effect. Using fura-2 loaded cells, PGE₂ (2 µmol/L), dibutyryl cAMP (2 mmol/L), and Ang II (2 µmol/L) increased intracellular calcium over basal concentrations by 5.5-fold, 3-fold, and 6.2-fold, respectively. Like PGE₂, dibutyryl cAMP also stimulated aldosterone release. PGE₂- and dibutyryl cAMP–induced aldosterone release were blocked by the calcium channel inhibitor diltiazem. These studies indicate that PGE₂ is a potent stimulus for aldosterone release and that the effect is mediated by EP₂ receptors. Both cAMP and calcium appear to mediate the steroidogenic effect of PGE₂ and calcium seems to be distal to cAMP.

Key Words: zona glomerulosa • cyclic AMP • calcium • receptors, prostanoid • angiotensin II

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