Chronic use of β2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of β-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo model of β2-adrenoceptor desensitization in guinea pig airways by administration of IL-1β intratracheally or chronic albuterol by inhalation. In the establishment of β-adrenoceptor desensitization in response to both β-agonist or inflammatory mediator, baseline pulmonary function responses were established to methacholine and isoproterenol-induced relaxation of methacholine bronchoconstriction. This was followed by the administration of IL-1β (500 IU/d intratracheally for 2 days) or chronic albuterol (0.1 g/L by aerosol for 1 min three times a day for 10 days). After administration, the methacholine and isoproterenol-methacholine response was once again evaluated. Intratracheal administration of IL-1β or chronic administration of albuterol significantly decreased (p <0.05) the protective effect of isoproterenol on methacholine-induced bronchoconstriction, eliciting β-adrenoceptor desensitization in vivo. The in vivo model will be very useful in monitoring the effect of other potential drugs on β-adrenoceptor function in the airways. Copyright (C) 1999 Elsevier Science Inc.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacological and Toxicological Methods|
|State||Published - Dec 1 1998|
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