The role of histamine in allergen and adenosine-induced bronchoconstriction

Abstract

We have investigated the role of histamine in allergen and adenosine-5'-monophosphate (AMP)-induced bronchoconstriction in asthmatic subjects by performing inhalation challenge tests with histamine, AMP and allergen after treatment with placebo or the potent H1 histamine receptor antagonist, terfenadine. Single concentrations of each agonist which had previously been shown to produce a 30% fall in FEV1 were used. After placebo, AMP and histamine both produced rapid bronchoconstriction reaching a maximum within 5 min and returning to within 10% of baseline after 25 min. Terfenadine inhibited this reaction to histamine completely and to AMP by 86%. The response to allergen was slower in onset and was sustained over 45 min and was inhibited 50% by terfenadine. We interpret these results as reflecting the contribution of histamine to the various airway challenges, both histamine and newly generated mediators comprise the response to allergen, whereas AMP selectively enhances mast cell degranulation without affecting the production of arachidonic acid derived mediators.