title: Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems.
abstract: 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.
authors.affiliation: C-3121 Medical Center North, Dept. of Medicine, Vanderbilt Univ., Nashville, TN 37232-4794, USA.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.forename: James A
authors.initials: JA
authors.lastname: McKanna
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004232:Diuretics / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007672:Kidney Cortex / Q000502:physiology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D004232:Diuretics; D015259:Dopamine Agents; D018491:Dopamine Agonists; D017673:Sodium Chloride, Dietary; D007980:Levodopa; C067113:SK&F 81297; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D004298:Dopamine