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Histamine inhibits activation of human neutrophils and HL-60 leukemic cells via H2-receptors

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Summary

The effects of prostaglandin E1 (PGE1) and histamine on activation of superoxide (O22/su−) formation, exocytosis of β-glucuronidase and aggregation in human neutrophils and HL-60 leukemic cells were studied. PGE1, histamine and impromidine, a potent H2-agonist, inhibited O2 − formation in neutrophils induced by the chemotactic peptide, N-formyl-l,-methionyl-l-leucyl-l-phenylalanine (fMet-Leu-Phe) with IC50 values of 0.5 µM, 8 µM and 2 µM, respectively. The full H1-agonist and weak partial H2-agonist, betahistine, was much less potent and effective than histamine. Dibutyryl cyclic AMP and forskolin mimicked the effects of histamine and PGE1, on O2 − formation. The H2-antagonist, famotidine, competitively reversed histamine-induced inhibition of O2 − formation with a pA2 value of 7.5. Histamine inhibited O2 − formation when added prior to or after fMet-Leu-Phe. fMet-Leu-Phe-induced aggregation and release of β-glucuronidase in neutrophils were less sensitive to inhibition by PGE1, histamine, dibutyryl cyclic AMP and forskolin thanOZ formation. The inhibitor of cyclic AMP-specific phosphodiesterase, rac-4-(3-butoxy4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724), additively enhanced the inhibitory effects of histamine and PGE1, on the above cell functions. In HL-60 cells differentiated by dimethyl sulfoxide or dibutyryl cyclic AMP, histamine, impromidine and PGE1, but not betahistine inhibited fMet-Leu-Phe-induced O2 − formation as well. Our data suggest that histamine inhibits activation of neutrophils and HL-60 cells via H2-receptors through activation of adenylyl cyclase and increased formation of cyclic AMP. As stimulated basophils and mast cells release high quantities of histamine, this intercellular signal molecule may play an inhibitory role in the activation of cytotoxic functions of myeloid cells.

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Authors and Affiliations

  1. Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69/73, D-1000, Berlin 33

    Rahel Burde, Roland Seifert & Günter Schultz

  2. Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2-4, D-1000, Berlin 33

    Armin Buschauerz

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  1. Rahel Burde
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  2. Roland Seifert
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  3. Armin Buschauerz
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  4. Günter Schultz
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Burde, R., Seifert, R., Buschauerz, A. et al. Histamine inhibits activation of human neutrophils and HL-60 leukemic cells via H2-receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 340, 671–678 (1989). https://doi.org/10.1007/BF00717743

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  • DOI: https://doi.org/10.1007/BF00717743

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