Inhibition of protein kinase C restores Na+,K(+)-ATPase activity in sciatic nerve of diabetic mice.
We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na+,K(+)-ATPase activity in the sciatic nerve of alloxan-induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na+,K(+)-ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na+,K(+)-ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4-9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half-life of approximately 1 h.
Hermenegildo
C
C
Instituto de Investigaciones Citológicas, Valencia, Spain.
Felipo
V
V
Miñana
M D
MD
Grisolía
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S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012584:Sciatic Nerve / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013449:Sulfonamides
D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase