title: Inhibition of H2 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 Ca(2+) concentration ([Ca(2+)](i)) in addition to an elevation of cAMP level in HL-60 promyelocytes. Here we show that the histamine-induced [Ca(2+)](i) rise was due to influx of Ca(2+) from the extracellular space, probably through nonselective cation channels, as incubation of the cells with SKF 96365 abolished the histamine-induced [Ca(2+)](i) rise, Na(+) influx, and membrane depolarization. The Ca(2+) 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 microM, respectively. Western blot analysis of protein kinase C (PKC) isoforms revealed that PMA (< or =1 nM) and ATP (300 microM) 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 [Ca(2+)](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.
authors.affiliation: Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: B C
authors.initials: BC
authors.lastname: Suh
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: D J
authors.initials: DJ
authors.lastname: Jun
authors.forename: J S
authors.initials: JS
authors.lastname: Chun
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: K T
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D002413:Cations, Divalent / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000201:enzymology; D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006131:Growth Inhibitors / Q000502:physiology; D018922:HL-60 Cells; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051745:Protein Kinase C-delta; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D006131:Growth Inhibitors; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D007527:Isoenzymes; D011970:Receptors, Histamine H2; D006632:Histamine; D000255:Adenosine Triphosphate; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D013755:Tetradecanoylphorbol Acetate