Protein kinase C-dependent stimulation of Na(+)-K(+)-ATP epsilon in rat proximal convoluted tubules

• Published in: The American journal of physiology Vol. 268; no. 5 Pt 1; p. C1277
• Main Authors: Féraille, E, Carranza, M L, Buffin-Meyer, B, Rousselot, M, Doucet, A, Favre, H
• Format: Journal Article
• Language: English
• Published: United States 01.05.1995
• Subjects: Animals; Enzyme Activation; Kidney Tubules, Proximal - enzymology; Male; Ouabain - pharmacology; Oxygen - pharmacology; Phorbol 12,13-Dibutyrate - pharmacology; Protein Kinase C - physiology; Rats; Rats, Wistar; Rubidium - pharmacokinetics; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1995.268.5.c1277

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.