Relation of Na+, K(+)-ATPase to delayed motor nerve conduction velocity: effect of aldose reductase inhibitor, ADN-138, on Na+, K(+)-ATPase activity.
The role of sorbitol, myo-inositol, and Na+, K(+)-adenosine triphosphatase (ATPase) activity on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-diabetic rats was studied. Reduction of MNCV and Na+, K(+)-ATPase in caudal nerves appeared after 3 weeks of diabetes, and at this time treatment with aldose reductase inhibitor (ARI), ADN-138 and 1% myo-inositol supplement was begun. One percent myo-inositol supplement for 3 weeks resulted in a significant increase in myo-inositol levels in diabetic nerves, but left MNCV and sorbitol levels unchanged. In contrast, treatment with ADN-138 for 3 weeks reduced sorbitol levels in diabetic nerves and resulted in significant increases in MNCV and Na+, K(+)-ATPase in the nerves. Since ADN-138 did not restore myo-inositol levels, the increase in Na+, K(+)-ATPase levels by ADN-138 treatment was independent of myo-inositol levels. Also, nerve Na+ levels in ADN-138-treated rats were reduced and the ratio of K+ to Na+ was raised, while 1% myo-inositol supplement did not affect them. These results suggest that treatment with ADN-138 elevates MNCV through a series of processes: ARI----reduction of sorbitol level----increase in Na+, K(+)-ATPase activity----correction of K+, Na+ imbalance----increase in MNCV.
Hirata
Y
Y
Central Research Laboratories, Kyorin Pharmaceutical Co, Ltd, Tochigi, Japan.
Okada
K
K
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology; D007294:Inositol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D009431:Neural Conduction / Q000187:drug effects; D010078:Oxazines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D013997:Time Factors
D010078:Oxazines; D011758:Pyrroles; D007294:Inositol; C054644:ADN 138; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase