beta-Adrenergic agonists and bronchial hyperreactivity: Role of beta(2)-adrenergic and tachykinin neurokinin-2 receptors

Background: beta(2)-Adrenergic agonists are the most widely used bronchodil ators for the treatment of asthma, On the other hand, there is concern that excessive use of beta(2)-agonists may contribute to the exacerbation of as thma. However, the mechanism of such adverse effects of beta(2)-agonists is not completely clear. Objective: The aim of this study was to assess the direct influence of beta (2)-agonists on airways by analyzing the effect of a beta(2)-agonist, fenot erol, 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 sensitiz ed guinea pigs that were exposed to daily inhalation of ovalbumin and fenot erol. We also investigated the effects of fenoterol on neurokinin-2 recepto r messenger RNA and density with Northern blot analysis and receptor bindin g assay. Result: The increase of airway responsiveness and the decrease of beta(2)-a drenergic receptors mere found in guinea pigs that mere treated with fenote rol. There were time- and dose-dependent increases of neurokinin-2 receptor mRNA and of density in tracheal smooth muscle that was treated with fenote rol. Conclusion: This increased airway responsiveness, increased neurokinin-2 re ceptor expression, and decreased beta(2)-adrenergic receptor density may be relevant to asthma exacerbation.