Direct stimulation of Na+-K+-ATPase and its glucosylated derivative by aldose reductase inhibitor.
In the presence of 10(-8) M concentrations of the aldose reductase inhibitor AL 1576, there is a 20-30% increase in the rate of hydrolysis of near-saturating concentrations of ATP by bovine renal Na+-K+-ATPase. When bovine renal Na+-K+-ATPase is reacted with glucose 6-phosphate in the presence of 10(-8) M concentrations of AL 1576 or 10(-6) M concentrations of a second aldose reductase inhibitor, sorbinil, glucosylation occurs. Whereas sorbinil has no effect on ATP hydrolysis by the glucosylated Na+-K+-ATPase, 10(-8) M AL 1576 causes a shift in the kinetics of hydrolysis of ATP from substrate inhibition to normal substrate activation. The aldose reductase inhibitors interact with the enzyme at the low-affinity ATP-binding site.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000494:pharmacology*; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins / Q000494:pharmacology; D006031:Glycosylation; D006827:Hydantoins / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007679:Kidney Medulla / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D013861:Thiocyanates / Q000494:pharmacology
D005449:Fluorenes; D005452:Fluoresceins; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D013861:Thiocyanates; C052241:imirestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; C026411:sorbinil; D016650:Fluorescein-5-isothiocyanate