DOPAMINE INHIBITS VASOPRESSIN-DEPENDENT CAMP PRODUCTION IN THE RAT CORTICAL COLLECTING DUCT

Dopamine inhibits Na+ and water reabsorption in the rat cortical colle cting duct (CCD) in the presence of arginine vasopressin (AVP). This i nhibition appears to involve the D-4 dopamine receptor isoform, which inhibits cAMP production; however, the D-1A receptor, which stimulates cAMP production, is also expressed in the CCD. To discriminate betwee n these opposing effects, we measured cAMP production in intact CCD se gments. The basal rate of cAMP production ranged from 6.5 to 10 fmol/m m of tubule length over a 7-min incubation period, and it was unaffect ed by either dopamine or the D-1A-specific agonist fenoldopam. AVP inc reased cAMP production to the range of 85-153 fmol.mm(-1).7 min(-1). W hereas neither 0.1 nor 1.0 mu M fenoldopam affected AVP-dependent cAMP production, dopamine reduced it in a dose-dependent manner, achieving a maximum inhibition of 50% at 10 mu M. This effect was reversed by t he D-4 receptor antagonist clozapine but not by pimozide or spiperone (antagonists of D-2 and D-3 receptors) or by calphostin C or cheleryth rine (inhibitors of protein kinase C). We conclude that dopamine inhib its transepithelial Na+ transport and osmotic water permeability in th e presence of AVP by inhibition of cAMP production, which is mediated by the D-4 receptor isoform linked via the inhibitory G protein G(i).