Protein kinase c-dependent stimulation of na,k-atpase in rat proximal
convoluted tubule.
Feraille, E., M. L. Carranza, B. Buffin-Meyer, M. Rousselot, A. Doucet, and H.
Favre.
Division de Nephrologie, Hopital Cantonal Universitaire, 24 rue Micheli du
Crest, 1211 Gen[grave]eve 14, Switzerland; Laboratoire de Physiologie
Cellulaire, Coll[grave]ege de France, 11 place M. Berthelot, 75231 Paris Cedex
5, France
APStracts 2:0054C, 1995.
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 sodium reabsorption. Because this inhibition occurs via phospholipase A2
activation, a pathway stimulated by hypoxia, we evaluated the influence of O2
supply on PKC action on Na+,K+-ATPase. Results confirmed that PDBU inhibited
PCT Na+,K+-ATPase activity under usual conditions. In contrast, when O2
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 sodium 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
ob served only under hypoxic conditions : It may represent an adaptation to
protect PCTs against deleterious effects of hypoxia.
Received 24 October 1994; accepted in final form 13 December 1994
APS Manuscript Number C0633-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.