Histamine increases cytosolic Ca2+ in dibutyryl-cAMP-differentiated HL-60 cells via H1 receptors and is an incomplete secretagogue.
Human neutrophils and dibutyryl-cAMP (Bt2cAMP)-differentiated HL-60 cells possess receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), which mediate activation of phospholipase C, with subsequent increase in cytosolic Ca2+ concentration ([Ca2+]i) and activation of specific cell functions. In many cell types, histamine, via H1 receptors, activates phospholipase C, but it is unknown whether neutrophilic cells possess functional H1 receptors. We compared the effects of histamine with those of fMet-Leu-Phe on activation of these cells. In Bt2cAMP-differentiated HL-60 cells, substances increased [Ca2+]i in the effectiveness order fMet-Leu-Phe greater than histamine greater than betahistine. Pertussis toxin diminished fMet-Leu-Phe-induced rises in [Ca2+]i to a greater extent than those induced by histamine. H1 but not H2 antagonists inhibited histamine- and betahistine-induced rises in [Ca2+]i. fMet-Leu-Phe and histamine activated phospholipase C and increased [Ca2+]i through release of Ca2+ from intracellular stores and sustained influx of Ca2+ from the extracellular space. The substances also induced Mn2+ influx. Ca2+ and Mn2+ influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl)-1H-imida zole hydrochloride (SK&F 96365). The stimulatory effects of histamine on [Ca2+]i were more sensitive to inhibition by 4 beta-phorbol 12-myristate 13-acetate than were those of fMet-Leu-Phe. Unlike fMet-Leu-Phe, histamine did not activate superoxide anion formation, release of beta-glucuronidase, and tyrosine phosphorylation. In neutrophils, histamine and betahistine did not induce rises in [Ca2+]i. Our data show that (i) in Bt2cAMP-differentiated HL-60 cells, histamine increases [Ca2+]i via H1 receptors coupled to pertussis toxin-sensitive and possibly, pertussis toxin-insensitive heterotrimeric regulatory guanine nucleotide-binding proteins, (ii) histamine activates nonselective cation channels, and (iii) unlike fMet-Leu-Phe, histamine is an incomplete secretagogue.
Seifert
R
R
Institut für Pharmakologie, Universitätsklinikum Rudolf Virchow, Freie Universität Berlin, Germany.
Höer
A
A
Offermanns
S
S
Buschauer
A
A
Schunack
W
W
D001621:Betahistine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D002454:Cell Differentiation / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002412:Cations; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D007473:Ion Channels; D011969:Receptors, Histamine H1; D010566:Virulence Factors, Bordetella; D013481:Superoxides; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D006632:Histamine; D037342:Pertussis Toxin; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D001621:Betahistine