Prostaglandin E ₂ –Induced Aldosterone Release Is Mediated by an EP ₂ Receptor

Abstract

Abstract-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 of aldosterone from cultured bovine adrenal zona glomerulosa cells. These studies were designed to determine whether this steroidogenic effect of PGE 2 was mediated by an EP 1 , EP 2 , or EP 3 receptor. Prostaglandin E 2 and 11-deoxy PGE 1 , an EP 2 -selective agonist, stimulated aldosterone release in a concentration-related manner with an ED 50 of 300 nmol/L for PGE 2 and 2 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 EP 1 -selective agonist, required concentrations of 100 mol/L to stimulate aldosterone release and sulprostone, an EP 3 /EP 1 -selective agonist, failed to alter aldosterone release. The EP 1 -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 ED 50 for PGE 2 was 9.8 mol/L. 17-Phenyl trinor PGE 2 and sulprostone were without effect. Using fura-2 loaded cells, PGE 2 (2 mol/L), dibutyryl cAMP (2 mmol/L), and Ang II (2 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 effect is mediated by EP 2 receptors. Both cAMP and calcium appear to mediate the steroidogenic effect of PGE 2 and calcium seems to be distal to cAMP. (Hypertension. 1998;31:575-581.)Key Words: zona glomerulosa Ⅲ cyclic AMP Ⅲ calcium Ⅲ receptors, prostanoid Ⅲ angiotensin II T here are five classes of prostanoid (P) receptors designated as EP, FP, DP, IP, and TP, corresponding to their naturally occurring agonists, prostaglandin E 2 , prostaglandin F 2␣ , prostaglandin D 2 , prostaglandin I 2 , and thromboxane A 2 , respectively.1 Synthetic and natural analogues of these prostaglandins also exist that possess selectivity at these five classes of receptors. 2,3The EP receptor has been subclassified into three subtypes: EP 1 , EP 2 , and EP 3 . [4][5][6][7][8] Based on the analysis of Coleman et al, 1,7 Eglin and Whiting, 3 and Muallem et al, 9 we know that prostanoid receptors differ in the second messengers that mediate their biological effects. Agonists acting on the EP 1 , FP, and TP receptors stimulate the IP 3 /DAG pathway and exert their effects through an increase in intracellular calcium. The EP 2 , DP, or IP receptor agonists stimulate adenylyl cyclase and the accumulation of cAMP. Finally, EP 3 receptor activation may increase IP 3 /DAG formation or inhibit adenylyl cyclase.There is considerable evid...

The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E 2

“…Cholesterol is then converted to pregnenolone by the P450 side-chain cleavage enzyme (35)(36)(37). AA and its metabolites play an essential role acting by regulating the rate-limiting step of steroidogenesis in different steroidogenic cells through its regulation of StAR protein expression in combination with cAMP (21,38). ACTH-induced steroidogenesis in the gland is mediated by Ca 2ϩ , cAMP, and AA metabolites.…”

The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

“…Unfortunately we have not measured the concentration of ATII and therefore a level of uncertainty exists with this interpretation. Other functional systems involved in aldosterone release, which have been reported to be changed in depression include arginin vasopressin [50,51] and prostaglandins, especially prostaglandin E2 [52-54]. …”

Distinct Roles of Central and Peripheral Prostaglandin E2 and EP Subtypes in Blood Pressure Regulation

“…78 The stimulation of aldosterone release in response to PGE 2 arises from the increased conversion of cholesterol to pregnenolone in the early step of aldosterone biosynthesis. The detailed signaling mechanism responsible for PGE 2 regulation of aldosterone release is unclear, but appears to involve cAMP-mobilizing EP 2 or EP 4 receptors.…”

“…The detailed signaling mechanism responsible for PGE 2 regulation of aldosterone release is unclear, but appears to involve cAMP-mobilizing EP 2 or EP 4 receptors. 78,79 roles of ep 1 /ep 3 …”