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

Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6):671-8. doi: 10.1007/BF00717743.


The effects of prostaglandin E1 (PGE1) and histamine on activation of superoxide (O2-) formation, exocytosis of beta-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 microM, 8 microM and 2 microM, 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 beta-glucuronidase in neutrophils were less sensitive to inhibition by PGE1, histamine, dibutyryl cyclic AMP and forskolin than O2- formation. The inhibitor of cyclic AMP-specific phosphodiesterase, rac-4-(3-butoxy-4-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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / pharmacology
  • Alprostadil / pharmacology
  • Bucladesine / pharmacology
  • Cell Aggregation
  • Cyclic AMP / metabolism
  • Exocytosis / drug effects
  • Glucuronidase / metabolism
  • Histamine / pharmacology*
  • Humans
  • Leukemia / metabolism*
  • Leukemia / pathology
  • N-Formylmethionine Leucyl-Phenylalanine / antagonists & inhibitors
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects*
  • Oxygen Consumption / drug effects
  • Receptors, Histamine H2 / drug effects
  • Receptors, Histamine H2 / physiology*
  • Superoxides / metabolism
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology


  • Receptors, Histamine H2
  • Superoxides
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
  • N-Formylmethionine Leucyl-Phenylalanine
  • Bucladesine
  • Histamine
  • Cyclic AMP
  • Glucuronidase
  • Alprostadil