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 D4 dopamine receptor isoform, which inhibits cAMP production; however, the D1A 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 D1A-specific agonist fenoldopam. AVP increased cAMP production to the range of 85-153 fmol . mm-1 . 7 min-1. Whereas neither 0.1 nor 1.0 microM fenoldopam affected AVP-dependent cAMP production, dopamine reduced it in a dose-dependent manner, achieving a maximum inhibition of 50% at 10 microM. This effect was reversed by the D4 receptor antagonist clozapine but not by pimozide or spiperone (antagonists of D2 and D3 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 D4 receptor isoform linked via the inhibitory G protein Gi.
Department of Physiology, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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D000470:Alkaloids; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D053119:Benzophenanthridines; D003024:Clozapine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D013134:Spiperone / Q000494:pharmacology; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; C493601:Drd4 protein, rat; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; C098593:dopamine D1A receptor; D001127:Arginine Vasopressin; D050638:Receptors, Dopamine D4; D010868:Pimozide; D015016:Yohimbine; D013134:Spiperone; D000242:Cyclic AMP; C016299:chelerythrine; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C058819:calphostin C; D018818:Fenoldopam; D003024:Clozapine; D004298:Dopamine; D004837:Epinephrine