Amelioration of nerve Na(+)-K(+)-ATPase activity independently of myo-inositol level by PGE1 analogue OP-1206.alpha-CD in streptozocin-induced diabetic rats.
An oral prostaglandin E1 (PGE1) analogue, OP-1206.alpha-CD, was given to rats with streptozocin (STZ)-induced diabetes to examine the therapeutic effects of OP-1206 on short-term and long-term diabetic neuropathy and its action mechanism with special reference to nerve Na(+)-K(+)-ATPase activity. In the short-term experiment, OP-1206 was administered daily to diabetic rats in 3- and 30-mg/kg doses for 4 wk from the day of STZ injection. In the long-term study, 10 micrograms/kg OP-1206 was also given daily for 8 wk from 7 mo after induction of diabetes. The compound improved decreased sciatic motor nerve conduction velocity in both short-term and long-term diabetic rats. The nerve Na(+)-K(+)-ATPase activity of diabetic rats, reduced by 40% compared with controls, was reversed to the level of controls in both experiments, whereas weight loss and hyperglycemia were unchanged, and neither nerve sorbitol accumulation nor myo-inositol depletion was corrected. In a morphometric analysis of myelinated nerve fibers (MNFs) in long-term diabetes, the mean diameter of the largest 10% of MNFs was significantly reduced in untreated diabetic compared with control rats, but OP-1206 completely reversed this reduction. The results suggest that OP-1206 ameliorates a decrease in nerve Na(+)-K(+)-ATPase activity without any effect on nerve myo-inositol level and that the compound may be not only a potent therapeutic agent for the treatment of diabetic neuropathy but also a useful research tool to investigate the mechanism of nerve Na(+)-K(+)-ATPase activity regulation.
Sonobe
M
M
Third Department of Medicine, Shiga University of Medical Science, Japan.
Yasuda
H
H
Hisanaga
T
T
Maeda
K
K
Yamashita
M
M
Kawabata
T
T
Kikkawa
R
R
Taniguchi
Y
Y
Shigeta
Y
Y
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D007294:Inositol / Q000378:metabolism*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000648:ultrastructure; D009431:Neural Conduction; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism
D001786:Blood Glucose; D011459:Prostaglandins E, Synthetic; D007294:Inositol; D013012:Sorbitol; C025090:ONO 1206; D000254:Sodium-Potassium-Exchanging ATPase; D000527:Alprostadil