Prostaglandin E-2 EP3 receptor regulates cyclooxygenase-2 expression in the kidney

Vio C.P.; Quiroz-Munoz, M; Cuevas C.A.; Cespedes, C; Ferreri N.R.

Abstract

Cyclooxygenase-2 (COX-2) is constitutively expressed and highly regulated in the thick ascending limb (TAL). As COX-2 inhibitors (Coxibs) increase COX-2 expression, we tested the hypothesis that a negative feedback mechanism involving PGE 2 EP3 receptors regulates COX-2 expression in the TAL. Sprague-Dawley rats were treated with a Coxib [celecoxib (20 mg·kg -1·day -1) or rofecoxib (10 mg·kg -1·day -1)], with or without sulprostone (20 (μg·kg -1·day -1). Sulprostone was given using two protocols, namely, previous to Coxib treatment (prevention effect; Sulp7-Coxib5 group) and 5 days after initiation of Coxib treatment (regression effect; Coxib10-Sulp5 group). Immunohistochemical and morphometric analysis revealed that the stained area for COX-2-positive TAL cells (μm 2/field) increased in Coxib-treated rats (Sham: 412 ± 56.3, Coxib: 794 ± 153.3). The Coxib effect was inhibited when sulprostone was used in either the prevention (285 ± 56.9) or regression (345 ± 51.1) protocols. Western blot analysis revealed a 2.1 ± 0.3-fold increase in COX-2 protein expression in the Coxib-treated group, an effect abolished by sulprostone using either the prevention (1.2 ± 0.3-fold) or regression (0.6 ± 0.4-fold vs. control, P < 0.05) protocols. Similarly, the 6.4 ± 0.6-fold increase in COX-2 mRNA abundance induced by Coxibs (P < 0.05) was inhibited by sulprostone; prevention: 0.9 ± 0.3-fold (P < 0.05) and regression: 0.6 ± 0.1 (P < 0.05). Administration of a selective EP3 receptor antagonist, L-798106, also increased the area for COX-2-stained cells, COX-2 mRNA accumulation, and protein expression in the TAL. Collectively, the data suggest that COX-2 levels are regulated by a novel negative feedback loop mediated by PGE2 acting on its EP3 receptor in the TAL. © 2012 the American Physiological Society.

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Título según WOS: Prostaglandin E-2 EP3 receptor regulates cyclooxygenase-2 expression in the kidney
Título según SCOPUS: Prostaglandin E 2 EP3 receptor regulates cyclooxygenase-2 expression in the kidney
Título de la Revista: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volumen: 303
Número: 3
Editorial: AMER PHYSIOLOGICAL SOC
Fecha de publicación: 2012
Página de inicio: F449
Página final: F457
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-84864774602&partnerID=40&md5=614031ff3155fec53d4ed67bf315caca
DOI:

10.1152/ajprenal.00634.2011

Notas: ISI, SCOPUS