Adenosine triphosphatase in nerves and ganglia of rats with streptozotocin-induced diabetes or galactosaemia; effects of aldose reductase inhibition

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Abstract
This study measured the ouabain-sensitive and ouabain-resistant adenosine triphosphatase activity in homogenates of the sciatic nerves and of pooled fourth and fifth lumbar dorsal root ganglia from rats fed 20% galactose or made diabetic with streptozotocin for either 4 or 8 weeks. Diabetes caused reductions in both fractions of sciatic nerve adenosine triphosphatase activity. After 8 weeks the ouabainsensitive fraction was 54% of control (ppppp<0.01)). In a group of rats fed galactose for 5 days, sciatic nerve ouabain-sensitive adenosine triphosphatase activity was 165% of control. Treatment with the aldose-reductase inhibitors tolrestat, ponalrestat or sorbinil prevented accumulation of polyol and depletion of myo-inositol in the sciatic nerves, indicating effective inhibition of aldose reductase. These drugs prevented completely the effect of galactose on the sciatic nerve adenosine triphosphatase activity, but had no significant effect on the reduction in adenosine triphosphatase activity in the sciatic nerves of diabetic rats. In the dorsal root ganglia galactose feeding had no measurable effect on the adenosine triphosphatase activity. Diabetes caused a modest numerical reduction in the ouabain-sensitive activity only. The findings indicate markedly different effects of diabetes and galactosaemia on the adenosine triphosphatase activity in rat sciatic nerve and show that the reduction in activity seen in the nerves of diabetic rats was not related to exaggerated polyol pathway flux.

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