title: The EP3 receptor regulates water excretion in response to high salt intake.
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-1·day-1) 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 PGE2levels 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-1·day-1), which increased COX-2 expression and renal PGE2production, 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 PGE2in 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 PGE2synthesis, thereby mitigating the inhibitory effects of PGE2on these transporters and decreasing urine volume.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York.
authors.forename: Shoujin
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Biology, Dominican College, Orangeburg, New York; and.
authors.forename: AnnMarie
authors.initials: A
authors.lastname: DelliPizzi
authors.affiliation: Department of Physiology, Center for Aging and Regeneration, CARE Chile UC, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile.
authors.forename: Mariana
authors.initials: M
authors.lastname: Quiroz-Munoz
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York.
authors.forename: Houli
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla, New York; nick_ferreri@nymc.edu.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Ferreri
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014867:Water / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D051399:Aquaporin 2; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012982:Sodium, Dietary; D014867:Water; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: AQP2; COX-2; EP3 receptors; PGE2; water homeostasis