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

Abstract

Histamine, through H-2 receptors, triggers a prominent rise in intracellular free Ca2+ concentration ([Ca2+](i)) in addition to an elevation of cAMP level 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 through nonselective cation channels, as incubation of the cells with SKF 96365 abolished the histamine-induced [Ca2+](i) rise, Na+ influx, and membrane depolarization. The Ca2+ influx was specifically inhibited by pretreatment of the cells with PMA or extracellular ATP with 50% inhibitory concentrations of 0.12 +/- 0.03 nM and 185 +/- 17 muM, respectively. Western blot analysis of protein kinase C (PKC) isoforms revealed that PMA (less than or equal to1 nM) and ATP (300 muM) caused selective translocation of PKC-delta to the particulate/membrane fraction. Costimulation of the cells with histamine and SKF 96365 partially reduced histamine-induced granulocytic differentiation, which was evaluated by looking at the extent of fmet-Leu-Phe-induced [Ca2+](i) rise and superoxide generation. In conclusion, nonselective cation channels are opened by stimulation of the H-2 receptor, and the channels are at least in part involved in the induction of histamine-mediated differentiation processes. Both effects of histamine were selectively inhibited probably by the delta isoform of PKC in HL-60 cells.