Inhibition of Na+,K(+)-ATPase in rat renal proximal tubules by dopamine involved DA-1 receptor activation.
Endogenous kidney dopamine (DA) causes natriuresis and diuresis, at least partly, via inhibition of proximal tubular Na+,K(+)-ATPase. The present study was done to identify the dopamine receptor subtype(s) involved in dopamine-induced inhibition of Na+,K(+)-ATPase activity. Suspensions of renal proximal tubules from Sprague-Dawley rats were incubated with dopamine, the DA-1 receptor agonist fenoldopam or the DA-2 receptor agonist SK&F 89124 in the presence or absence of either the DA-1 receptor antagonist SCH 23390 or the DA-2 receptor antagonist domperidone. Dopamine and fenoldopam (10(-5) to 10(-8) mol/l) produced a concentration-dependent inhibition of Na+,K(+)-ATPase activity. However, SK&F 89124 failed to produce any significant effect over the same concentration range. Incubation with fenoldopam (10(-5) to 10(-8) mol/l) in the presence of SK&F 89124 (10(-6) mol/l) inhibited Na+,K(+)-ATPase activity to a degree similar to that with fenoldopam alone. Furthermore, DA-induced inhibition of Na+,K(+)-ATPase activity was attenuated by SCH 23390, but not by domperidone. Since alpha-adrenoceptor activation is reported to stimulate Na+,K(+)-ATPase activity and, at higher concentrations, dopamine also acts as an alpha-adrenoceptor agonist, the potential opposing effect from alpha-adrenoceptor activation on DA-induced inhibition of Na+,K(+)-ATPase activity was investigated by using the alpha-adrenoceptor blocker phentolamine. We found that, in the lower concentration range (10(-5) to 10(-7) mol/l), dopamine-induced inhibition of Na+,K(+)-ATPase activity in the presence of phentolamine was similar in magnitude to that observed with dopamine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
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Department of Pharmacology, College of Pharmacy, University of Houston, Texas 77204-5515.
Lokhandwala
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MF
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D018818:Fenoldopam; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D009761:Nystatin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D007211:Indoles; D017447:Receptors, Dopamine D1; D009761:Nystatin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C047183:SK&F 89124; D000254:Sodium-Potassium-Exchanging ATPase; D018818:Fenoldopam; D004298:Dopamine