Expression of Prostaglandin E Receptor EP₄ Subtype in Rat Adrenal Zona Glomerulosa

Involvement in Aldosterone Release

Abstract

We examined the role of prostaglandin (PG) E receptors in the secretion of aldosterone. PGE₂ is known to exert its various biological functions by binding to PGE receptors. There are four subtypes of PGE receptors, EP₁, EP₂, EP₃, and EP₄. Among the PGE receptors EP₂ and EP₄ subtypes are coupled to Gs protein and stimulate adenylyl cyclase. In this study, PGE₂ caused a dose-dependent increase in aldosterone production from the rat adrenal zona glomerulosa cells in vitro accompanied with an increase in intracellular cAMP concentration. A specific agonist for EP₂, butaprost, did not increase the cAMP production or the aldosterone release, suggesting the possibility that EP₄ mediates the secretion of aldosterone by PGE₂. Northern blot hybridization analysis disclosed that EP₄ gene was expressed in the rat adrenal gland but that EP₂ gene was not. In situ hybridization revealed that EP₄ mRNA is present abundantly in the zona glomerulosa of rat adrenal gland. These findings suggest that the PGE₂-EP₄ system is involved in the regulation of aldosterone secretion from the rat adrenal gland.