Urea inhibition of renal (NA+ + K+)ATPase activity is reversed by cAMP.
In the present work we studied the modulation of the effect of urea on the renal (Na+ + K+)ATPase by cAMP. We observed that urea inhibits the (NA+ + K+)ATPase activity in a dose-dependent manner, reaching 60% of inhibition at the concentration of 1M. This effect was completely reversed by dibutyryl-cAMP (dBcAMP) at 5 x 10(-4)M. The effect of dBcAMP was mimicked by 50 units of the catalytic subunit of protein kinase A and completely abolished by 5 x 10(-7)M H89, an inhibitor of protein kinase A. Addition of 1M urea decreases basal phosphorylation of the immunoprecipitated (NA+ + K+)ATPase in 50%, with this effect completely reversed by 5 x 10(-4)M dBcAMP. Furthermore, 5 x 10(-4)M dBcAMP by itself induced (NA+ + K+)ATPase phosphorylation. Taken together these data indicate that cAMP could be, in addition to the organic solutes already known, an important physiological modulator of the deleterious effect of urea on enzyme activity.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000502:physiology*; D007679:Kidney Medulla / Q000201:enzymology*; D007700:Kinetics; D010766:Phosphorylation; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D014508:Urea / Q000494:pharmacology*
D003994:Bucladesine; D014508:Urea; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase