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

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'.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Benko R,Molnar TF,Szombati V,Benkö I,Bartho L

doi

10.1159/000440769

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

253-5

issue

5-6

eissn

0031-7012

issn

1423-0313

pii

000440769

journal_volume

96

pub_type

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