Dopamine inhibits vasopressin action in the rat inner medullary collecting duct via alpha(2)-adrenoceptors.
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 microM). Clozapine (10 microM), a dopamine D(4) 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 microM) 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.
Edwards
R M
RM
Department of Renal/Urology Biology, GlaxoSmithKline, King of Prussia, Pennsylvania 19406-0939, USA. richard_m_edwards@gsk.com
Brooks
D P
DP
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007679:Kidney Medulla / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D018341:Receptors, Adrenergic, alpha-2; D014667:Vasopressins; D015016:Yohimbine; D000242:Cyclic AMP; D003024:Clozapine; D004298:Dopamine; D009638:Norepinephrine