Dopamine inhibits vasopressin-dependent cAMP production in the rat cortical collecting duct

Dopamine inhibits Na and water reabsorption in the rat cortical collecting duct (CCD) in the presence of arginine vasopressin (AVP). This inhibition appears to involve the D dopamine receptor isoform, which inhibits cAMP production; however, the D receptor, which stimulates cAMP production, is also expressed in the CCD. To discriminate between these opposing effects, we measured cAMP production in intact CCD segments. The basal rate of cAMP production ranged from 6.5 to 10 fmol/mm of tubule length over a 7-min incubation period, and it was unaffected by either dopamine or the D -specific agonist fenoldopam. AVP increased cAMP production to the range of 85-153 fmol ⋅ mm ⋅ 7 min . Whereas neither 0.1 nor 1.0 μM fenoldopam affected AVP-dependent cAMP production, dopamine reduced it in a dose-dependent manner, achieving a maximum inhibition of 50% at 10 μM. This effect was reversed by the D receptor antagonist clozapine but not by pimozide or spiperone (antagonists of D and D receptors) or by calphostin C or chelerythrine (inhibitors of protein kinase C). We conclude that dopamine inhibits transepithelial Na transport and osmotic water permeability in the presence of AVP by inhibition of cAMP production, which is mediated by the D receptor isoform linked via the inhibitory G protein G .