Dopamine inhibits vasopressin action in the rat inner medullary collectingduct via alpha(2)-adrenoceptors

We compared the effects of dopamine and norepinephrine on vasopressin (AVP) -stimulated increases in osmotic water permeability (Pf) and cAMP accumulat ion in the rat inner medullary collecting duct (IMCD). Both dopamine and no repinephrine inhibited AVP-induced Pf and cAMP accumulation in a concentrat ion-dependent manner; however, norepinephrine was approximately 100-fold mo re potent than dopamine. The effects of dopamine on Pf were antagonized by the selective alpha (2)-adrenoceptor antagonist, rauwolscine (10 nM-1 muM). Clozapine (10 muM), a dopamine D-4 receptor antagonist with significant ac tivity at adrenergic receptors, partially attenuated both dopamine and nore pinephrine-induced decreases in AVP-stimulated Pf. Dopamine-induced inhibit ion of AVP-dependent cAMP levels was antagonized by the alpha (2)-adrenocep tor antagonists, rauwolscine, idazoxan, and yohimbine, but not by the dopam ine receptor antagonists, spiperone, SCH-23390, or raclopride. Clozapine (1 -10 muM) inhibited the effects of both dopamine and norepinephrine on AVP-s timulated cAMP levels. We conclude that the inhibitory effects of dopamine on AVP-induced Pf and cAMP accumulation in the rat IMCD are mediated via ad renoceptors.