An in vivo model of beta-adrenoceptor desensitization

Chronic use of beta2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of beta-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo model of beta2-adrenoceptor desensitization in guinea pig airways by administration of IL-1beta intratracheally or chronic albuterol by inhalation. In the establishment of beta-adrenoceptor desensitization in response to both beta-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-1beta (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-1beta or chronic administration of albuterol significantly decreased (p < 0.05) the protective effect of isoproterenol on methacholine-induced bronchoconstriction, eliciting beta-adrenoceptor desensitization in vivo. The in vivo model will be very useful in monitoring the effect of other potential drugs on beta-adrenoceptor function in the airways.