Protein kinase C-dependent stimulation of Na(+)-K(+)-ATP epsilon 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 A2 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 86Rb+ uptake. This latter effect, which was abolished by PKC inhibitors, resulted from an increment of the Na+ 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.
Féraille
E
E
Division de Néphrologie, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Carranza
M L
ML
Buffin-Meyer
B
B
Rousselot
M
M
Doucet
A
A
Favre
H
H
D000818:Animals; D004789:Enzyme Activation; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D015240:Phorbol 12,13-Dibutyrate; D010042:Ouabain; D012964:Sodium; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D010100:Oxygen