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

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Abstract
Diacylglycerol and phorbol esters activate protein kinase C in intact cells. Addition of the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG) to quiescent cultures of Swiss [mouse] 3T3 cells caused a marked increase in the rate of ouabain-sensitive 86Rb+ uptake, a measure of the activity of th Na+/K+ pump. The effect was dose-dependent and cound 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 h) 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. 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.