Stimulation of glucosylated lens epithelial Na,K-ATPase by an aldose reductase inhibitor.
In diabetes, glucosylation of the Na,K-ATPase of the lens epithelium makes the pump inefficient. K+ transport and ATP hydrolysis (at near saturating ATP concentrations) are inhibited and the kinetics of ATP hydrolysis become substrate inhibition type. The AR inhibitor (AL1576, Alcon Laboratories) stimulates K+ transport and ATP hydrolysis by glucosylated bovine lens Na,K-ATPase. This inhibitor has a slight stimulatory effect upon the unmodified enzyme function also. The AR inhibitor is not able to prevent glucosylation of the pump in high-glucose-containing medium.
Garner
M H
MH
Department of Ophthalmology, California College of Medicine, University of California, Irvine 92717.
Wang
G M
GM
Spector
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004848:Epithelium / Q000201:enzymology; D005449:Fluorenes / Q000037:antagonists & inhibitors*; D005947:Glucose / Q000378:metabolism; D006827:Hydantoins / Q000037:antagonists & inhibitors*; D007908:Lens, Crystalline / Q000201:enzymology*; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D005449:Fluorenes; D006827:Hydantoins; C052241:imirestat; D000255:Adenosine Triphosphate; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D011188:Potassium