Prostaglandin E2-induced aldosterone release is mediated by an EP2 receptor. Hypertension 1998 Feb;31(2):575-81
Date
02/14/1998Pubmed ID
9461224DOI
10.1161/01.hyp.31.2.575Scopus ID
2-s2.0-0031594322 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
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 micromol/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 micromol/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 micromol/L. 17-Phenyl trinor PGE2 and sulprostone were without effect. Using fura-2 loaded cells, PGE2 (2 micromol/L), dibutyryl cAMP (2 mmol/L), and Ang 11 (2 micromol/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.
Author List
Csukas S, Hanke CJ, Rewolinski D, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinCraig J. Hanke PhD Assistant Dean, Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adrenal GlandsAldosterone
Angiotensin II
Animals
Bucladesine
Calcium
Cattle
Cells, Cultured
Cyclic AMP
Dinoprostone
Female
Intracellular Membranes
Prostaglandins
Receptors, Cell Surface
Zona Glomerulosa