BACKGROUND: beta(2)-Adrenergic agonists are the most widely used bronchodilators 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 asthma. 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, 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 beta(2)-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 beta(2)-adrenergic receptor density may be relevant to asthma exacerbation.
BACKGROUND:beta(2)-Adrenergic agonists are the most widely used bronchodilators 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 asthma. 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, 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 beta(2)-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 beta(2)-adrenergic receptor density may be relevant to asthma exacerbation.
Authors: A Helisch; E Schirrmacher; O Thews; R Schirrmacher; H G Buchholz; W Dillenburg; S Höhnemann; J Tillmanns; I Wessler; R Buhl; F Rösch; P Bartenstein Journal: Eur J Nucl Med Mol Imaging Date: 2005-08-31 Impact factor: 9.236