TPA induces cytoplasmic alkalinization in human monoblastic U-937 cells without activation of Na+/H+ exchange.
The effect of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on cytoplasmic pH (pHi) and H+ extrusion was studied in the human monoblastic cell line U-937. About 2 min after addition of TPA, pHi started to increase and reached a steady state 10-15 min later. The resulting alkalinization corresponded to 0.03 and 0.09 pH units at 10(-10) and 10(-7) M TPA, respectively. The TPA-induced increase in pHi was independent of the presence of extracellular Na+. Moreover, TPA did not affect the H+ extrusion from the U-937 cells. Together these observations indicate the presence of a novel mechanism for TPA-induced cytoplasmic alkalinization. This mechanism is independent of Na+/H+ exchange across the plasma membrane, but may involve organelle sequestration of H+.
D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008223:Lymphoma; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D006859:Hydrogen; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate