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 stimulatory effect of PKC on Na+ reabsorption. Because this inhibition occurs 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 activity under usual conditions. In contrast, when oxygen supply was increased, PDBu had no effect on Na+-K+-ATPase hydrolytic activity, but it dose-dependently stimulated ouabain-sensitive Rb-86(+) uptake. This latter effect, which was abolished by PKC inhibitors, resulted from an increment of the Naf sensitivity of Na+-K+-ATPase. Thus, in oxygenated rat PCTs, activation of PKC primarily stimulated Na+-K+-ATPase. This likely 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.