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. K(m) 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 G(s)-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 G(i)-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.