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Vol. 298, Issue 3, 1001-1006, September 2001

Dopamine Inhibits Vasopressin Action in the Rat Inner Medullary Collecting Duct via alpha 2-Adrenoceptors

Richard M. Edwards and David P. Brooks

Department of Renal/Urology Biology, GlaxoSmithKline, King of Prussia, Pennsylvania

We compared the effects of dopamine and norepinephrine on vasopressin (AVP)-stimulated increases in osmotic water permeability (Pf) and cAMP accumulation in the rat inner medullary collecting duct (IMCD). Both dopamine and norepinephrine inhibited AVP-induced Pf and cAMP accumulation in a concentration-dependent manner; however, norepinephrine was approximately 100-fold more potent than dopamine. The effects of dopamine on Pf were antagonized by the selective alpha 2-adrenoceptor antagonist, rauwolscine (10 nM-1 µM). Clozapine (10 µM), a dopamine D4 receptor antagonist with significant activity at adrenergic receptors, partially attenuated both dopamine and norepinephrine-induced decreases in AVP-stimulated Pf. Dopamine-induced inhibition of AVP-dependent cAMP levels was antagonized by the alpha 2-adrenoceptor antagonists, rauwolscine, idazoxan, and yohimbine, but not by the dopamine receptor antagonists, spiperone, SCH-23390, or raclopride. Clozapine (1-10 µM) inhibited the effects of both dopamine and norepinephrine on AVP-stimulated cAMP levels. We conclude that the inhibitory effects of dopamine on AVP-induced Pf and cAMP accumulation in the rat IMCD are mediated via alpha 2-adrenoceptors.

0022-3565/01/2983-1001$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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