DA1 receptor mediated regulation of Na(+)-H+ antiport activity in rat renal cortical brush border membrane vesicles.
Our previous studies indicate that dopamine (DA) plays an important role in regulating renal sodium (Na+) metabolism during high Na+ intake, and that DA1 receptors are involved in natriuretic response to acute volume expansion. It has also been shown that in addition to the changes in renal hemodynamics, the natriuretic response produced by exogenously administered DA and DA1 receptor agonists appears to be due to alterations in renal tubular sodium transport mechanisms. This study was designed to investigate the DA1 receptor-mediated changes in Na(+)-H+ antiport activity in tubular brush border membranes of rat kidney. The Na(+)-H+ antiport activity, measured as the amiloride-sensitive Na+ influx in BBMV, was inhibited by 37%, 46%, 33%, and 42% by 1 microM DA, SKF 82958, SKF 38393, and fenoldopam respectively. The DA1 antagonist SCH 23390 increased the antiport activity when given alone, while when administered with an agonist it attenuated the effects of the agonist on the antiporter. DA2 agonists and antagonists failed to affect the antiport activity. These results indicate that the inhibitory effects of DA and DA receptor agonists on Na(+)-H+ antiport activity in renal cortical BBMV were mediated by the DA1 receptors.
College of Pharmacy & Health Sciences, Texas Southern University, Houston 77004.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D018818:Fenoldopam; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017923:Sodium-Hydrogen Exchangers; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000584:Amiloride; D012964:Sodium; D018818:Fenoldopam; D004298:Dopamine