Prostaglandin E 2 –Induced Aldosterone Release Is Mediated by an EP 2 Receptor
| Autor: | Craig J. Hanke, David Rewolinski, Stephen Csukas, William B. Campbell |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Prostaglandin E2 receptor Receptors Cell Surface Biology Dinoprostone chemistry.chemical_compound Internal medicine Adrenal Glands Cyclic AMP Internal Medicine medicine Animals Prostaglandin E2 Aldosterone Cells Cultured Angiotensin II Calcium channel Intracellular Membranes medicine.anatomical_structure Endocrinology Bucladesine chemistry Mineralocorticoid Zona glomerulosa Prostaglandins Calcium Cattle Female Zona Glomerulosa medicine.drug |
| Zdroj: | Hypertension. 31:575-581 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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