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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Apr;82(8):2384–2388. doi: 10.1073/pnas.82.8.2384

Ionic responses rapidly elicited by activation of protein kinase C in quiescent Swiss 3T3 cells.

F Vara, J A Schneider, E Rozengurt
PMCID: PMC397562  PMID: 2581246

Abstract

Diacylglycerol and phorbol esters activate protein kinase C in intact cells. We report here that addition of the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG) to quiescent cultures of Swiss 3T3 cells caused a marked increase in the rate of ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na+/K+ pump. The effect was dose-dependent and could be detected after 1 min of exposure to the diacylglycerol. OAG stimulated Na+ influx via an amiloride-sensitive pathway and increased intracellular pH by 0.15 pH unit. Phorbol 12,13-dibutyrate (PBt2) also enhanced ouabain-sensitive 86Rb+ uptake and amiloride-sensitive 22Na+ influx. Prolonged treatment (40 hr) of 3T3 cells with PBt2 at a saturating dose, which reduces the number of PBt2 binding sites and protein kinase C activity, abolished the ionic response of the cells to a subsequent addition of either OAG or PBt2. Appropriate controls using acid "loads" and the Na+ ionophore monensin showed that the function of the Na+/H+ antiport system and of the Na+/K+ pump was not impaired in the PBt2-desensitized cells. We suggest that activation of protein kinase C elicits, either directly or indirectly, enhanced Na+/H+ antiport activity, which, in turn, leads to Na+ influx, intracellular pH modulation, and stimulation of the Na+/K+ pump.

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Selected References

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