Phorbol esters induce differentiation in a pre-B-lymphocyte cell line by enhancing Na+/H+ exchange.
The murine pre-B-lymphocyte cell line 70Z /3 may be induced to differentiate to a surface immunoglobulin-positive phenotype by the polyclonal B-cell mitogen, lipopolysaccharide. This is accomplished via activation of an amiloride-sensitive Na+-uptake system ( Rosoff , P. M., and Cantley , L. C. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 7547-7550). Here we show that the active tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) also induces surface IgM expression in 70Z /3 cells. TPA also appears to work by activating a plasma membrane Na+/H+ exchange system. A significant increase in cellular Na+ was detected within 10 min after TPA addition and by 2 h an 80% increase was observed. Amiloride blocked both the induction of surface IgM and the increase in cellular Na+. Further evidence that both TPA and lipopolysaccharide activate Na+/H+ exchange was provided by measurements of intracellular pH with carboxyfluorescein. Both TPA and lipopolysaccharide caused a 0.15 unit increase in cytoplasmic pH within 5 min after addition to the cells at 37 degrees C. The pH change required high extracellular Na+ and was inhibited by amiloride. These data suggest a mechanism by which phorbol esters affect cellular growth and differentiation.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D002454:Cell Differentiation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008070:Lipopolysaccharides; D010704:Phorbols; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D012964:Sodium; D000251:Adenosine Triphosphatases; C022761:potassium transporting ATPase; C021838:sodium-translocating ATPase; D013755:Tetradecanoylphorbol Acetate