Inhibition of the chemotactic peptide-induced elevation of intracellular calcium in differentiated human leukemic (HL-60) cells by the phorbol ester phorbol 12-myristate 13-acetate.
The chemotactic peptide formylmethionylleucylphenylalanine rapidly elevated the intracellular calcium concentration, in a concentration-dependent manner, of human leukemic (HL-60) cells which had been differentiated to polymorphonuclear leukocyte-like cells by pretreatment with dimethyl sulfoxide (1.3%). Preincubation of the cells with phorbol 12-myristate 13-acetate, a protein kinase C-activating phorbol ester, inhibited the formylmethionylleucylphenylalanine-induced rise in intracellular calcium in a time- and concentration-dependent manner. 4 alpha-Phorbol 12,13-didecanoate, which does not activate protein kinase C, was inactive in this capacity. The use of calcium-free medium suggested that the elevation of intracellular calcium by formylmethionylleucylphenylalanine consisted of rapid intracellular release followed by calcium influx. Phorbol 12-myristate 13-acetate (10(-7) M) inhibited both components of the elevation of intracellular calcium, whereas 10(-8) M phorbol 12-myristate 13-acetate inhibited only the calcium influx. The influx of calcium was not prevented by verapamil, which blocks the voltage-dependent calcium channels. These data suggest that, in differentiated HL-60 cells, 12-O-tetradecanoylphorbol-13-acetate rapidly inhibits both the intracellular release of calcium and calcium influx through non-voltage-dependent calcium channels in response to formylmethionylleucylphenylalanine.
D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007295:Inositol Phosphates; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium