Inhibition of H2 Histamine Receptor-Mediated Cation Channel Opening by Protein Kinase C in Human Promyelocytic Cells

Abstract

Histamine, through H2 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 μM, respectively. Western blot analysis of protein kinase C (PKC) isoforms revealed that PMA (≤1 nM) and ATP (300 μM) caused selective translocation of PKC-δ 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 H2 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 δ isoform of PKC in HL-60 cells.

Biomic study of human myeloid leukemia cells differentiation to macrophages using DNA array, proteomic, and bioinformatic analytical methods

“…In our experiment, retinoic acid receptor RXR-alpha was downregulated during HL-60 cells differentiation to macrophages same as that by Kumar et al [45]. TPA caused selective translocation of PKC-delta to the particulate and membrane fraction [46]. Treatment of human myeloid leukemia cells with TPA, an activator of protein kinase C (PKC), is associated with induction of monocytic differentiation.…”

Histamine facilitates GABAergic transmission in the rat entorhinal cortex: Roles of H1 and H2 receptors, Na+‐permeable cation channels, and inward rectifier K+ channels

“…The reductions seen in interneuron I K are likely due to the activation of H 2 (Atzori et al, ), whereas H 1 ‐mediated depolarization is linked to inhibition of Kirs (He et al, ). The activation of a TTX‐insensitive Na + permeable channel is also likely due to H 1 activity (Gorelova and Reiner, ; Bell et al, ); however, H 2 may also increase Na + influx via a non‐selective cation channel, as seen is in promyelocytes (Suh et al, ). Future work using selective receptor agonists and methods to isolate particular ionic mechanisms will be helpful in clarifying the roles of H 1 and H 2 in HA‐induced activation of TTX‐insenstive Na + currents and inhibition of Kirs/ I K .…”

Leumorphin has an anti‐apoptotic effect by activating epidermal growth factor receptor kinase in rat pheochromocytoma PC12 cells

“…Intracellular cAMP generation was determined by [ 3 H]cAMP competition assay as previously described (Suh et al . 2001).…”

“…The crystals were dissolved in dimethylsufoxide, and the absorbance values of the samples were measured at 570 nm. cAMP measurement Intracellular cAMP generation was determined by [ 3 H]cAMP competition assay as previously described (Suh et al 2001). Serum-deprived PC12 cells were pre-treated with the phosphodiesterase inhibitor Ro 20-1724 (5 lM) for 15 min, and stimulated with agonists for 10 min in the presence of Ro 20-1724.…”