Adenosine triphosphatase in nerves and ganglia of rats with streptozotocin-induced diabetes or galactosaemia; effects of aldose reductase inhibition.
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 ouabain-sensitive fraction was 54% of control (p less than 0.05) and the ouabain-resistant fraction was 57% of control (p less than 0.05). Galactose feeding more than doubled the ouabain-sensitive adenosine triphosphatase activity in the sciatic nerve (225% of control after 4 weeks, 215% of control after 8 weeks of galactose feeding, both p less than 0.01) and produced a progressive increase in the ouabain-resistant fraction (119% of control at 4 weeks (p less than 0.05) and 176% of control at 8 weeks (p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lambourne
J E
JE
Department of Physiology and Pharmacology, Medical School, University of Nottingham, UK.
Brown
A M
AM
Calcutt
N
N
Tomlinson
D R
DR
Willars
G B
GB
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001834:Body Water / Q000032:analysis; D001835:Body Weight; D002241:Carbohydrates / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005693:Galactosemias / Q000201:enzymology*; D005727:Ganglia, Spinal / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000201:enzymology* / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D002241:Carbohydrates; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000251:Adenosine Triphosphatases