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.
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)
Seifert
R
R
Institut für Pharmakologie, Universitätsklinikum Rudolf Virchow, Freie Universität Berlin, Germany.
Grünbaum
L
L
Schultz
G
G
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D037342:Pertussis Toxin; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017442:Histamine Agonists; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D011969:Receptors, Histamine H1; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium