Inhibition of H-2 histamine receptor-mediated cation channel opening by protein kinase C in human promyelocytic cells

Histamine, through H-2 receptors, triggers a prominent rise in intracellula r free Ca2+ concentration ([Ca2+](i)) in addition to an elevation of cAMP l evel in HL-60 promyelocytes. Here we show that the histamine-induced [Ca2+] (i) rise was due to influx of Ca2+ from the extracellular space, probably t hrough nonselective cation channels, as incubation of the cells with SKF 96 365 abolished the histamine-induced [Ca2+](i) rise, Na+ influx, and membran e depolarization. The Ca2+ influx was specifically inhibited by pretreatmen t of the cells with PMA or extracellular ATP with 50% inhibitory concentrat ions of 0.12 +/- 0.03 nM and 185 +/- 17 muM, respectively. Western blot ana lysis of protein kinase C (PKC) isoforms revealed that PMA (less than or eq ual to1 nM) and ATP (300 muM) caused selective translocation of PKC-delta t o the particulate/membrane fraction. Costimulation of the cells with histam ine and SKF 96365 partially reduced histamine-induced granulocytic differen tiation, which was evaluated by looking at the extent of fmet-Leu-Phe-induc ed [Ca2+](i) rise and superoxide generation. In conclusion, nonselective ca tion channels are opened by stimulation of the H-2 receptor, and the channe ls are at least in part involved in the induction of histamine-mediated dif ferentiation processes. Both effects of histamine were selectively inhibite d probably by the delta isoform of PKC in HL-60 cells.