β-Adrenergic agonists and bronchial hyperreactivity: Role of β2- adrenergic and tachykinin neurokinin-2 receptors

Abstract

Background: β2-Adrenergic agonists are the most widely used bronchodilators for the treatment of asthma. On the other hand, there is concern that excessive use of β2-agonists may contribute to the exacerbation of asthma. However, the mechanism of such adverse effects of β2-agonists is not completely clear. Objective: The aim of this study was to assess the direct influence of β2-agonists on airways by analyzing the effect of a β2-agonist, fenoterol, on airway sensitivity in an animal model and on tachykinin neurokinin-2 receptor expression in bovine tracheal smooth muscle. Methods: We performed an acetylcholine challenge test on ovalbumin sensitized guinea pigs that were exposed to daily inhalation of ovalbumin and fenoterol. We also investigated the effects of fenoterol on neurokinin-2 receptor messenger RNA and density with Northern blot analysis and receptor binding assay. Result: The increase of airway responsiveness and the decrease of β2-adrenergic receptors were found in guinea pigs that were treated with fenoterol. There were time- and dose-dependent increases of neurokinin-2 receptor mRNA and of density in tracheal smooth muscle that was treated with fenoterol. Conclusion: This increased airway responsiveness, increased neurokinin-2 receptor expression, and decreased β2-adrenergic receptor density may be relevant to asthma exacerbation.