Affiliation:
1. From the Medical College of Wisconsin, Departments of Ophthalmology and Pharmacology and Toxicology, Milwaukee, Wis.
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 μmol/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 μmol/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 μmol/L. 17-Phenyl trinor PGE
2
and sulprostone were without effect. Using fura-2 loaded cells, PGE
2
(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 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Reference37 articles.
1. Coleman RA Kennedy I Humphrey PPA Bunce K Lumley P. Prostanoids and their receptors. In: Hanseh C Sammes PG Taylor JB eds. Comprehensive Medicinal Chemistry. Vol 3. Oxford: Pergamon Press; 1990:643–714.
2. Coleman RA Kennedy I Sheldrick RLG. New evidence with selective agonists and antagonists for the subclassification of PGE 2 -sensitive (EP) receptors. In: Samuelsson B Paoletti R Ramwell PW eds. Advances in Prostaglandin Thromboxane and Leukotriene Research. Vol 17. Ann Arbor Mich: Books on Demand; 1987:467–470.
3. Eglin RM Whiting RL. Classification of prostanoid receptors. In: Willis AL ed. CRC Handbook of Eicosanoids: Prostaglandins and Related Lipids. Vol 2. Boca Raton Fla: CRC Press; 1989:273–289.
4. Cloning and expression of cDNA for a mouse EP1 subtype of prostaglandin E receptor.
5. Cloning and expression of a cDNA for mouse prostaglandin E receptor EP2 subtype.
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