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

Naunyn Schmiedebergs Arch Pharmacol. 1994 Apr;349(4):355-61. doi: 10.1007/BF00170880.


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 1 alpha,25-dihydroxycholecalciferol. In HL-60 monocytes, HA increased [Ca2+]i with a half-maximal effect at 8 microM and a maximum at 30-100 microM. 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 beta-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-(beta-[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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Calcium / metabolism*
  • Cell Line
  • GTP-Binding Proteins / metabolism*
  • Histamine / pharmacology
  • Histamine Agonists / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Monocytes / metabolism*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Oxygen Consumption / drug effects
  • Pertussis Toxin
  • Platelet Aggregation Inhibitors / pharmacology
  • Receptors, Histamine H1 / drug effects
  • Receptors, Histamine H1 / metabolism*
  • Virulence Factors, Bordetella / pharmacology


  • Histamine Agonists
  • Imidazoles
  • Platelet Aggregation Inhibitors
  • Receptors, Histamine H1
  • Virulence Factors, Bordetella
  • Adenosine Diphosphate Ribose
  • N-Formylmethionine Leucyl-Phenylalanine
  • Histamine
  • Pertussis Toxin
  • GTP-Binding Proteins
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Calcium