The inhibition of sodium, potassium-stimulated ATPase and corneal swelling: the role played by polyols.
BACKGROUND
Sodium, potassium-stimulated adenosine triphosphatase (Na,K-ATPase; E. C. 3.6.1.37) is considered to be the principal corneal enzyme responsible for deturgescence. Some metabolites are known to inhibit Na,K-ATPase, including glucose and galactose. In diabetes, some cells take up high levels of glucose and are converted to the polyhydroxy alcohol: sorbitol. In galactosemia, a similar uptake of galactose may cause the intracellular formation of the polyhydroxy alcohol: galactatol. This study tested the possibility that polyhydroxy alcohols (polyols), metabolized from carbohydrates, might decrease Na,K-ATPase activity.


METHODS
Cultured corneal endothelial cells were separately exposed to 20 mM of the polyols: sorbitol, galactitol, and xylitol. Media containing 5 mM glucose served as the control. Plasma membrane vesicles, containing the Na,K-ATPase, were isolated and tested for the enzyme's activity.


RESULTS
We found that the enzyme, after exposure to polyols, had only 15%-20% of its normal activity when assayed with the control.


CONCLUSIONS
Since corneal endothelial cells can generate polyols in diabetes mellitus, this result may explain why corneas are able to swell in individuals with poorly controlled diabetes.
Whikehart
D R
DR
Vision Science Research Center, School of Optometry, University of Alabama at Birmingham 35294, USA.
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015715:Corneal Edema / Q000201:enzymology* / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D004728:Endothelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004376:Galactitol / Q000494:pharmacology*; D006801:Humans; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013012:Sorbitol / Q000494:pharmacology*; D014993:Xylitol / Q000494:pharmacology*
D004376:Galactitol; D013012:Sorbitol; D000254:Sodium-Potassium-Exchanging ATPase; D014993:Xylitol