NYMC Faculty Publications

The EP3 Receptor Regulates Water Excretion in Response to High Salt Intake

Author Type(s)

Faculty

DOI

10.1152/ajprenal.00589.2015

Journal Title

American Journal of Physiology. Renal Physiology

First Page

F822

Last Page

F829

Document Type

Article

Publication Date

10-1-2016

Keywords

AQP2, COX-2, EP3 receptors, PGE2, water homeostasis

Disciplines

Medicine and Health Sciences

Abstract

The mechanisms by which prostanoids contribute to the maintenance of whole body water homeostasis are complex and not fully understood. The present study demonstrates that an EP3-dependent feedback mechanism contributes to the regulation of water homeostasis under high-salt conditions. Rats on a normal diet and tap water were placed in metabolic cages and given either sulprostone (20 μg·kg·day) or vehicle for 3 days to activate EP3 receptors in the thick ascending limb (TAL). Treatment was continued for another 3 days in rats given either 1% NaCl in the drinking water or tap water. Sulprostone decreased expression of cyclooxygenase 2 (COX-2) expression by ∼75% in TAL tubules from rats given 1% NaCl concomitant with a ∼60% inhibition of COX-2-dependent PGE levels in the kidney. Urine volume increased after ingestion of 1% NaCl but was reduced ∼40% by sulprostone. In contrast, the highly selective EP3 receptor antagonist L-798106 (100 μg·kg·day), which increased COX-2 expression and renal PGE production, increased urine volume in rats given 1% NaCl. Sulprostone increased expression of aquaporin-2 (AQP2) in the inner medullary collecting duct plasma membrane in association with an increase in phosphorylation at Ser269 and decrease in Ser261 phosphorylation; antagonism of EP3 with L-798106 reduced AQP2 expression. Thus, although acute activation of EP3 by PGE in the TAL and collecting duct inhibits the Na-K-2Cl cotransporter and AQP2 activity, respectively, chronic activation of EP3 in vivo limits the extent of COX-2-derived PGE synthesis, thereby mitigating the inhibitory effects of PGE on these transporters and decreasing urine volume.

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