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J Am Soc Nephrol 12:649-658, 2001
© 2001 American Society of Nephrology

Induction of Cyclooxygenase-2 in Thick Ascending Limb Cells by Adrenalectomy

CARLOS P. VIO*, SHAO-JIAN AN{dagger}, CARLOS CÉSPEDES*, JOHN C. MCGIFF{dagger} and NICHOLAS R. FERRERI{dagger}

* Departamento de Ciencias Fisiologicas, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
{dagger} Department of Pharmacology, New York Medical College, Valhalla, New York.

Correspondence to Dr. Nicholas R. Ferreri, Department of Pharmacology, New York Medical College, Valhalla, NY 10595. Phone: 914-594-4079; Fax: 914-347-4956; E-mail: nick_ferreri{at}nymc.edu

Abstract. Adrenalectomized (ADX) and sham-operated rats received either dexamethasone (DEX) or vehicle. Renal tissue was used for morphologic analysis, assessment of cyclooxygenase-2 (COX-2) protein expression and mRNA accumulation, and quantitation of COX-2 activity. In untreated or shamoperated rats, COX-2 protein was observed in a subset of tubular epithelial cells (<2%), which were located mainly in the cortex. All COX-2-positive cells also expressed Tamm-Horsfall glycoprotein, a highly selective marker for thick ascending limb (TAL) cells. After ADX, >30% of TAL cells expressed COX-2 in a manner consistent with recruitment of COX-2-positive TAL cells toward the medulla. Treatment of ADX rats with DEX reduced the number of COX-2-positive cells to that observed in sham-operated or intact rats. COX-2 mRNA accumulation was increased by ADX and partially attenuated by treatment with DEX. Western blot analysis of cortical microsomes revealed a substantial increase in COX-2 expression in ADX rats, compared with ADX/DEX-treated, sham-operated, or intact rats. The increase in COX-2 protein expression was associated with a twofold increase in prostaglandin E2 formation by cortical microsomes obtained from ADX rats, compared with sham-operated rats. It is concluded that ADX induces expression of enzymatically active COX-2, such that expression occurs in the cortical TAL and proceeds in a defined pattern toward the outer medullary TAL. It is suggested that ADX induces expression of TAL cells that, in the basal state, do not express COX-2 protein.




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