Ionic responses rapidly elicited by activation of protein kinase C in quiescent Swiss 3T3 cells.
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.
Vara
F
F
Schneider
J A
JA
Rozengurt
E
E
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D004075:Diglycerides; D007473:Ion Channels; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D010042:Ouabain; D000584:Amiloride; C038237:1-oleoyl-2-acetylglycerol; D012964:Sodium; D011494:Protein Kinases; D011493:Protein Kinase C; D012413:Rubidium; D011188:Potassium