Inhibition by pertussis toxin of the activation of Na(+)-dependent uridine transport in dimethyl-sulphoxide-induced HL-60 leukaemia cells.
The effects of pertussis toxin on the Na(+)-dependent transport of uridine were studied in HL-60 leukaemia cells induced to differentiate along the granulocytic or monocytic pathways by dimethyl sulphoxide (DMSO) or phorbol 12-myristate 13-acetate (PMA) respectively. Pertussis toxin at 50 ng/ml completely inhibited the activation of Na(+)-dependent uridine transport and consequently prevented the formation of intracellular pools of free uridine which occurs in HL-60 cells induced to differentiate by DMSO. The inhibition of Na(+)-dependent uridine transport by pertussis toxin in cells exposed to DMSO was associated with a 14-fold decrease in affinity, with no change in Vmax. Pertussis toxin, however, had no effect on Na(+)-dependent uridine transport in PMA-induced HL-60 cells. Furthermore, 500 ng of cholera toxin/ml had no effect on the Na(+)-dependent uptake of uridine in DMSO-treated HL-60 cells. These results suggest that the activation of the Na(+)-dependent transport of uridine in HL-60 cells induced to differentiate along the granulocytic pathway by DMSO is coupled to a pertussis-toxin-sensitive guanine-nucleotide binding protein (G-protein).
Sokoloski
J A
JA
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Sartorelli
A C
AC
Handschumacher
R E
RE
Lee
C W
CW
D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000473:pathology; D037342:Pertussis Toxin; D012964:Sodium / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D012964:Sodium; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; D014529:Uridine; D004121:Dimethyl Sulfoxide