Effect of SK&F 96365 on extracellular Ca2+ -dependent O2- production in neutrophil-like HL-60 cells

Store-operated Ca2+ entry is referred to a capacitative current activated by Ca2+ -stores depletion in various non-excitable cells. Neutrophil-like HL-60 cells responded to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP) by an early O2- production preceded by a [Ca2+]i rise. Cell stimulation in the absence of extracellular Ca2+ resulted in a major reduction of [Ca2+]i rise and O2- production. A purported inhibitor of store-operated Ca2+ entry, SK&F 96365 (1-(beta-(3-(4-methoxy-phenyl)propoxyl)-4-methoxy-phenetyl)- 1H-imidazole hydrochloride), inhibited extracellular Ca2+ -dependent [Ca2+]i rise by 30% but did not alter O2- production. In conclusion, SK&F 96365 did not modify extracellular Ca2+ -dependent O2- production, despite a significant but limited reduction in fMLP-activated membrane Ca2+ fluxes which can be ascribed to store-operated Ca2+ entry. Furthermore, Ca2+ influx is necessary for a full induction and maintenance of the biological response.