Combined Inhibition of Histamine H1 Receptors and Leukotrienes Reduces Compound 48/80-Induced Contraction of the Human Bronchus in vitro

Rita Benko, Tamas F. Molnar, Veronika Szombati, István Benkö, Lorand Bartho

Research output: Contribution to journalArticle

Abstract

Background/Aims: Bronchial asthma continues to be a big challenge to therapy. Mast cells play an important role in allergic asthma. Histamine and leukotrienes are established mast cell mediators, but antihistamines currently play no role in asthma therapy. Methods: Human bronchial strips were exposed to the mast cell activator compound 48/80 (200 μg/ml) in isolated organ experiments. Results: The contractile response was not inhibited by the H1 receptor antagonist antihistamine chloropyramine (0.3 μmol/l), the leukotriene cys-LT1 receptor antagonist MK 571 (3 μmol/l), the 5-lipoxygenase inhibitor MK 886 (5 μmol/l), the cyclo-oxygenase inhibitor indomethacin (5 μmol/l), tetrodotoxin, or atropine. Chloropyramine, combined with either MK 571 or MK 886 significantly reduced the response. Conclusion: A supra-additive effect is proposed for the antihistamine and the anti-leukotrienes, which might have relevance to human asthma therapy as well; such a combination deserves a large-scale clinical study. These data also indicate that substances like compound 48/80 should be denoted as mast cell activators rather than 'histamine liberators'.

Original languageEnglish
Pages (from-to)253-255
Number of pages3
JournalPharmacology
Volume96
Issue number5-6
DOIs
Publication statusPublished - Nov 1 2015

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Keywords

  • Antileukotrienes
  • Bronchus (human)
  • Compound 48/80
  • Histamine
  • Histamine antagonist

ASJC Scopus subject areas

  • Pharmacology

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