Differentiation of renal Na(+)-K(+)-ATPase in control and streptozotocin-induced diabetic mice by G-protein acting toxins and phorbol esters.
The specific activity of Na(+)-K(+)-ATPase in the renal medulla and cortex of 50-day-old streptozotocin (STZ)-induced diabetic mice was increased 58% and 50%, respectively, as compared to controls. Km values of Na+ and K+ for this enzyme were unaltered, while that of ATP was decreased in diabetic mice. The Na(+)-K(+)-ATPase in control medulla and cortex was activated by both cholera and pertussis toxins, while this effect was abolished in diabetics. Since dibutyryl cAMP stimulates cortical Na(+)-K(+)-ATPase activity in control mice, the activation effect of cholera toxin on this enzyme might be due to its interaction with a Gs-protein and the persistent stimulation of adenylate cyclase activity, while the effect of pertussis toxin might be due to its masking of the inhibitory action of a Gi-protein on adenylate cyclase activity. However, the protein kinase C (PKC)-associated Na(+)-K(+)-ATPase might also be quiescent in diabetes, because the stimulating effect of phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on this enzyme was abolished in diabetic cortex. In addition, nicardipine and ouabain were found to have differential effects on this enzyme derived from control and diabetic mice.
Chen
C C
CC
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, ROC.
D037361:Adenylate Cyclase Toxin; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D007672:Kidney Cortex / Q000201:enzymology*; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009529:Nicardipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D015240:Phorbol 12,13-Dibutyrate; D010042:Ouabain; D003994:Bucladesine; D002772:Cholera Toxin; D009529:Nicardipine; D037342:Pertussis Toxin; D000254:Sodium-Potassium-Exchanging ATPase; D013755:Tetradecanoylphorbol Acetate