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Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems

George O'Brien Center for Kidney and Urologic Diseases, and ¹Departments of Medicine and ²Cell and Developmental Biology, Vanderbilt University School of Medicine and Department of Veterans Affairs Medical Center, Nashville, Tennessee

Submitted 28 June 2004 ; accepted in final form 9 December 2004

In mammalian kidney, dopamine produced in the proximal tubule (PT) acts as an autocrine/paracrine natriuretic hormone that inhibits salt and fluid reabsorption in the PT. In high-salt-treated animals, PT dopamine activity increases and inhibits reabsorption, leading to increased salt and fluid delivery to the macula densa (MD) and subsequent natriuresis and diuresis. Regulated cyclooxygenase-2 (COX-2) in the MD represents another intrinsic system mediating renal salt and water homeostasis. Renal cortical COX-2 is inversely related to salt intake, and decreased extracellular NaCl stimulates COX-2 expression in cultured MD/cortical thick ascending limb cells. The current study investigated interactions between renal dopamine and cortical COX-2 systems. In rats fed a control diet, the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) or the DA1 receptor agonist SKF-81297 suppressed cortical COX-2 expression. High salt suppressed cortical COX-2 expression, which was attenuated by inhibition of dopamine production with benserazide or the DA1 receptor antagonist, SCH-23390. In contrast, L-DOPA or the dopamine-metabolizing enzyme inhibitor entacapone suppressed low-salt-induced cortical COX-2 expression. Inhibition of PT reabsorption with the carbonic anhydrase inhibitor acetazolamide suppressed cortical COX-2 expression. In contrast, treatment with distally acting diuretics led to elevation of cortical COX-2. These results indicate that dopamine modulates renal cortical COX-2 expression by modifying PT reabsorption.

prostaglandin synthase G₂/H₂; cortex; proximal tubule reabsorption

This article has been cited by other articles:

				B. Yao, J. Xu, Z. Qi, R. C. Harris, and M.-Z. Zhang Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake Am J Physiol Renal Physiol, August 1, 2006; 291(2): F368 - F374. [Abstract] [Full Text] [PDF]