Abstract
Proliferation‐associated changes in calcium metabolism were investigated employing the promyelocytic HL‐60 and monoblastic U‐937 cell lines. The cells were stimulated to proliferate employing mitogenic factors as follows. 1) Transferrin or insulin: HL‐60 cells were adjusted for growth in serum‐free medium, and 24 h prior to the experiment, the cells were deprived of transferrin or insulin. The re‐addition of either one of them stimulated cell proliferation as was evident by increased [^3^H]‐tymidine incorporation activity. Cell proliferation was associated with an enhanced Ca^2+^ influx rate, measured by ^45^Ca^2+^ uptake activity. 2) Granulocyte‐monocyte colony‐stimulating factor (GM‐CSF): addition of GM‐CSF to proliferating or quiescent HL‐60 cells resulted in increased cell proliferation, which was also accompanied by increased rate of Ca^2+^ influx. 3) Serum: HL‐60 and U‐937 were grown for 24 h in serum‐depleted medium. Re‐addition of serum to the cells was not associated with immediate or delayed change in calcium influx rate but rather with an immediate increase in the cytosolic free calcium concentration, measured employing the fluorescent probe, fura‐2AM. This increase was independent of extracellular calcium, unaffected by verapamil, diltiazem, and lanthanum, and associated with enhanced ^45^Ca^2+^ efflux. Thus, in all three cases evoked cell proliferation was accompanied by quantitative changes in Ca^2+^ metabolism. While the transferrin‐, insulin‐, and GM‐CSF‐stimulated cell proliferation was accompanied by delayed increases in ^45^Ca^2+^ influx, the serumstimulated cell proliferation was accompanied by an immediate elevation of free cytosolic Ca^2+^.