Premium
Activation of EP3 receptors suppresses COX‐2 in thick ascending limb (TAL) and inhibits water excretion
Author(s) -
Hao Shoujin,
DelliPizzi AnnMarie,
Jiang Houli,
QuirozMunoz Mariana,
Cespedes Carlos,
Knepper Mark,
Vio Carlos,
Ferreri Nicholas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.809.21
Subject(s) - chemistry , nephron , receptor , medicine , endocrinology , kidney , aquaporin 2 , in vivo , excretion , antagonist , cyclooxygenase , biology , enzyme , biochemistry , mechanical engineering , microbiology and biotechnology , water channel , engineering , inlet
We previously showed that inhibition of EP3 receptors (EP3r) enhances cyclooxygenase‐2 (COX‐2) expression in the TAL, suggesting that the level of COX‐2 is regulated by an EP3r‐dependent negative feedback mechanism in this segment of the nephron. The contribution of this mechanism to the regulation of water excretion was determined in vivo by activating EP3r with sulprostone. 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. Treatment was continued for another 3 days in rats given 1% NaCl in the drinking water or tap water. The induction of COX‐2 expression observed in TAL tubules from rats given 1% NaCl decreased approximately 75% with sulprostone, which also inhibited renal COX‐2‐dependent PGE2 content by ~60% (LC/MS/MS analysis). Urine volume increased with 1% NaCl but was reduced ~40% by sulprostone (n=4, p<0.05). In contrast, the EP3r antagonist (L‐798106, 100 µg/kg/day), which increased COX‐2 expression in the TAL, increased urine volume in rats given either tap water or 1% NaCl. Sulprostone increased expression of the non‐glycosylated and glycosylated forms of AQP2 in inner medullary collecting duct. The increase in AQP2 expression was confirmed by immunofluorescence microscopy. EP3r activation in the TAL and CD would be predicted to inhibit NKCC2 and AQP2, respectively, and increase urine volume. However, targeted activation of EP3r limits the extent of COX‐2‐derived PGE2 synthesis thereby disrupting the projected effects of PGE2 on NKCC2 and AQP2 and decreasing urine volume.