We have reported that the vasotropic agent, prostaglandin E
1 analogue OP1206·α-CD (OP) ameliorates the decrease in sciatic motor nerve conduction velocity (MCV) and Na
+/K
+-ATPase activity of rats with streptozocin-induced diabetes without normalizing abnormal nerve sorbitol or myo-inositol content. This observation suggests that nerve Na
+/K
+-ATP-ase activity may be regulated by unknown metabolites other than myo-inositol. In order to examine this possibility, the effect of OP on Na
+/K
+-ATPase activity was examined in vitro.
Twenty-seven 8-week-old Sprague-Dawley rats were used in the experiment. Diabetes mellitus was induced by intravenous injection of streptozocin 45 mg/kg. Six weeks after the injection, the diabetic rats had significantly higher levels of plasma glucose, lower body weights and slower sciatic motor nerve conduction velocities than the control rats (all p<0.001). Sciatic nerves isolated six weeks after treatment were incubated with various concentrations of OP: the decreased Na
+/K
+-ATPase activity was ameliorated in a dose-dependent manner, and the improvement was significant at concentrations higher than 0.5ng/ml in the diabetic rats. Nerve cAMP concentrations were also increased in a dose-dependent manner in the diabetic rats.
These rasults suggest that OP has a direct effect on diabetic nerve tissue via a mechanism which might be associated with an increase in nerve cAMP levels rather than a vasotropic action.
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