BIPHASIC AND DIFFERENTIAL MODULATION OF CA2-60 CELLS( ENTRY BY ATP AND UTP IN PROMYELOCYTIC LEUKEMIA HL)

ATP and UTP cause mobilization of Ca2+ from the intracellular stores w ith similar potency in several cell types including both undifferentia ted and differentiated HL60 cells. We show here that, in HL60 cells wi th Ca2+ stores that had been fully and irreversibly emptied using the endomembrane Ca2+-ATPase inhibitor thapsigargin, both nucleotides prod uced a biphasic effect on Ca2+ entry, first rapid inhibition and then delayed (about 15 s) activation. ATP was more effective at producing t he initial inhibition of Ca2+ entry, whereas UTP was more effective at activating the delayed Ca2+ entry. Previous incubation with UTP desen sitized the Ca2+ mobilization and the delayed activation of Ca2+ entry induced by ATP but not the inhibition of Ca2+ entry. The ATP analogue 2-methylthioATP (2-MeSATP) barely mobilized stored Ca2+ but inhibited Ca2+ entry. These results could be explained by the presence of two r eceptors: (i) a P-2u receptor sensitive to ATP and UTP, responsible fo r activation of phospholipase C and Ca2+ mobilization, early inhibitio n of Ca2+ entry and delayed activation of Ca2+ entry and (ii) a P-2y-l ike receptor sensitive to ATP and 2-MeSATP which produces only inhibit ion of Ca2+ entry. The inhibition of Ca2+ entry by nucleotides increas ed greatly during differentiation. Given that Ca2+ mobilization by nuc leotides is not modified by differentiation, this suggests that a comp onent of the mechanism of inhibition of Ca2+ entry is gradually expres sed during differ entiation of HL60 cells.