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

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• 作者：Toshio Katsunuma ; Kazunobu Fujita ; Judith C.W. Mak ; Peter J. Barnes ; Kozo Ueno ; Yoji Iikura
• 关键词：Asthma ; β ; ₂-adrenergic receptor ; neurokinin-2 receptor
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2000
• 出版时间：July 2000
• 年：2000
• 卷：106
• 期：1, Supplement 1
• 页码：S104-S108
• 全文大小：112 K

文摘

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. (J Allergy Clin Immunol 2000;106:S104-8.)