Amelioration of nerve Na(+)-K(+)-ATPase activity independently of myo-inositol level by PGE1 analogue OP-1206.alpha-CD in streptozocin-induced diabetic rats.

Abstract

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.

• Authors: M Sonobe, H Yasuda, T Hisanaga, K Maeda, M Yamashita, T Kawabata, R Kikkawa, Y Taniguchi, Y Shigeta
• Journal: Diabetes (Diabetes) Vol. 40 Issue 6 Pg. 726-30 (Jun 1991) ISSN: 0012-1797 [Print] United States
• PMID: 1645681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Prostaglandins E, Synthetic
• Inositol
• Sorbitol
• ONO 1206
• Sodium-Potassium-Exchanging ATPase
• Alprostadil

Topics

• Alprostadil (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, physiopathology)
• Inositol (metabolism)
• Male
• Motor Neurons (drug effects, metabolism, physiology)
• Nerve Fibers, Myelinated (drug effects, ultrastructure)
• Neural Conduction
• Prostaglandins E, Synthetic (therapeutic use)
• Rats
• Rats, Inbred Strains
• Reference Values
• Sciatic Nerve (drug effects, metabolism, physiopathology)
• Sodium-Potassium-Exchanging ATPase (metabolism)
• Sorbitol (metabolism)