The histamine receptor 2 may be a pacemaker for neutrophil activation

W. K. Kim-Park, M. A. Moore, M. J. Kowolik

Research output: Contribution to journalArticle

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Abstract

There is considerable debate regarding the relative contributions of the histamine (HA) H1 and H2 receptors in neutrophil activation. The effects of HA-ligands on human neutrophils were assayed by luminol-dependent chemiluminescence (CL) and analyzed by a two-tailed paired Student's t-test. Histamine alone did not significantly alter the CL generation, but the H1-antagonist (phenylenediamine, 10-6 M) inhibited histamine- or FMLP-mediated CL significantly (p < 0.01). An H2-antagonist, cimetidine (10-6 M), partially inhibited the FMLP-mediated CL generation with slight stimulation of histamine-mediated CL. H1-antagonist and H2-agonist, dB-c-AMP, together produced the same degree of inhibition of FMLP challenge seen with H1-antagonist. A significant sensitivity of HA to EGTA-, H1-antagonist- or quinacrine-treatment (p < 0.01) indicated the H1-receptor mediated activation of phospholipase C (PLC) may require extracellular Ca2+. The histamine-mediated CL was also sensitive to inhibitors of protein kinase C (PKC) and tyrosine kinase (TK), indicating a Ca2+-mediated phosphorylation. Further, HA-mediated CL generation was partially inhibited by a G-protein blocker, pertussis toxin (PTX). We conclude that histamine receptor 1-mediated neutrophil activation via the PLC pathway may be modulated via H2-site cascade in a G-protein dependent manner.

Original languageEnglish (US)
Pages (from-to)383-396
Number of pages14
JournalInflammopharmacology
Volume8
Issue number4
DOIs
StatePublished - Dec 1 2000

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Keywords

  • Cyclic AMP
  • FMLP
  • Histamine
  • Neutrophil
  • Phospholipase C
  • Signal transduction

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

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