Histamine H1-receptors in HL-60 monocytes are coupled to Gi-proteins and pertussis toxin-insensitive G-proteins and mediate activation of Ca2+ influx without concomitant Ca2+ mobilization from intracellular stores

  • Roland Seifert
  • Lore Grünbaum
  • Günter Schultz
Article

Abstract

The results of binding studies suggest the presence of histamine H1-receptors in human monocytes, but it is not known whether these receptors are functionally active. This prompted us to study the effects of histamine (HA) on cytosolic Ca2+ concentration ([Ca2+]i) and superoxide anion (O2 ) formation in HL-60 cells differentiated towards monocytes with 1α,25-dihydroxychole-calciferol. In HL-60 monocytes, HA increased [Ca2+]i with a half-maximal effect at 8 μM and a maximum at 30–100 μM. Pertussis toxin (PTX) partially inhibited the stimulatory effects of HA on [Ca2+]i. Betahistine, a weak partial H1-receptor agonist, also increased [Ca2+]i, whereas H2- and H3-receptor agonists were ineffective. H1- but not H2- and H3-receptor antagonists inhibited HA induced rises in [Ca2+]i. HA-induced rises in [Ca2+]i were desensitized in a homologous manner and were also inhibited by the activator of protein kinase C, 4\-phorbol 12-myristate 13-acetate. Various protein kinase C inhibitors did not interfere with homologous desensitization. The stimulatory effects of HA on [Ca2+]i were completely dependent on the presence of extracellular Ca2+ and were inhibited by the blocker of non-selective cation (NSC) channels, 1-{\-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl}-1 H-imidazole hydrochloride (SK & F 96365). HA was much less effective than the chemotactic peptide, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), to induce rises in [Ca2+]i. Unlike fMLP, HA did not activate O2 formation. Our data indicate that HL-60 monocytes possess H1-receptors coupled to heterotrimeric regulatory guanine nucleotide-binding proteins (G-proteins) of the Gi-family and PTX-insensitive G-proteins which mediate activation of NSC channels without concomitant activation of Ca2+ mobilization from intracellular stores, that homologous desensitization of HA-induced Ca2+ influx is independent of protein kinase C and that the stimulatory effect of HA on Ca2+ influx is too small to result in activation of O2 formation.

Key words

HL-60 monocytes Histamine H1-receptors G-proteins Pertussis toxin Non-selective cation channels Superoxide anion formation 

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Roland Seifert
    • 1
  • Lore Grünbaum
    • 1
  • Günter Schultz
    • 1
  1. 1.Institut für Pharmakologie, Universitätsklinikum Rudolf VirchowFreie Universität BerlinBerlinGermany

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