Effect of L-DOPA, dopamine, dihydroxyphenyl acetic acid and homovanillic acid on Na,K-ATPase activity in rat proximal tubule segments.
We have recently demonstrated that dopamine (DA) inhibits Na,K-ATPase in single proximal tubule (PCT) segments dissected from previously collagenase perfused rat kidney. The aim of the present study was to ascertain whether this effect was directly mediated by DA or if DA was the precursor of an inhibitor. When PCT segments were incubated with L-DOPA, Na,K-ATPase was significantly lower than in vehicle incubated tubules. Inhibition of dopa decarboxylase abolished the effect of L-DOPA on Na,K-ATPase activity. The metabolites of DA, 3, 4-dihydroxphenyl acetic acid (DPAC) and homovanillic acid (HVA) both inhibited Na,K-ATPase activity in doses higher than 10(-6) M. Both HVA and DPAC 10(-4) M caused approximately 35% inhibition. Dopamine inhibited Na,K-ATPase activity even in a dose as low as 10(-7) M. Maximal inhibition (greater than 60%) was found with DA-5 M. Na,K-ATPase activity was significantly lower in tubules exposed to DA 10(-4) and 10(-5) M than in tubules exposed to DPAC or HVA 10(-4) and 10(-5) M. Dopamine produced in proximal tubule cells from L-DOPA, is an active inhibitor of the Na,K-pump in these cells. The DA metabolites DPAC and HVA are less potent Na,K-pump-inhibitors.
Bertorello
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Aperia
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D010648:Phenylacetates; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine; D006719:Homovanillic Acid