Evidence for involvement of protein kinase C in regulation of intracellular pH by Cl-/HCO-3 antiport.
The activity of the main base-extruding mechanism in Vero cells, the Na(+)-independent Cl-/HCO-3 antiport, increases 5- to 10-fold when the cytosolic pH (pHi) is increased over a narrow range close to neutrality. We have studied the effect on this regulation of stimulation and inhibition of protein kinase C by short-term and long-term treatment with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). After short-term treatment with TPA to stimulate the kinase, the threshold value for activation of the antiport is shifted to a more acidic pH. After prolonged treatment with TPA to downregulate protein kinase C the sensitivity of the antiport to variation in proton concentration was lowered, possibly by reducing the number of essential proton-binding sites. Concomitantly, the steady state pHi of the cells was increased. The data indicate that protein kinase C is involved in the regulation of the Na(+)-independent Cl-/HCO-3 antiport.
Ludt
J
J
Institute for Cancer Research, Norwegian Radium Hospital, Montebello, Oslo.
Tønnessen
T I
TI
Sandvig
K
K
Olsnes
S
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014709:Vero Cells
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate