PROTEIN-KINASE C-DEPENDENT STIMULATION OF NA-K+-ATPASE IN RAT PROXIMAL CONVOLUTED TUBULES()

In rat proximal convoluted tubule (PCT), activation of protein kinase C (PKC) by phorbol 12,13-dibutyrate (PDBu) was previously reported to inhibit Na+-K+-ATPase, a paradoxical finding in view of the known stim ulatory effect of PKC on Na+ reabsorption. Because this inhibition occ urs via phospholipase A(2) activation, a pathway stimulated by hypoxia , we evaluated the influence of oxygen supply on PKC action on Na+-K+- ATPase. Results confirmed that PDBu inhibited PCT Na+-K+-ATPase activi ty under usual conditions. In contrast, when oxygen supply was increas ed, PDBu had no effect on Na+-K+-ATPase hydrolytic activity, but it do se-dependently stimulated ouabain-sensitive Rb-86(+) uptake. This latt er effect, which was abolished by PKC inhibitors, resulted from an inc rement of the Naf sensitivity of Na+-K+-ATPase. Thus, in oxygenated ra t PCTs, activation of PKC primarily stimulated Na+-K+-ATPase. This lik ely contributes to increase solute reabsorption. Inhibition of Na+-K+- ATPase was observed only under hypoxic conditions. It may represent an adaptation to protect PCTs against deleterious effects of hypoxia.