An in vivo model of beta-adrenoceptor desensitization

Chronic use of beta(2)-agonists and increased production of inflammatory me diators during the late allergic reaction after antigen challenge results i n the desensitization of beta-adrenoceptors in the airways and the accompan ying rise in nonspecific airway hyperresponsiveness. In this study, we esta blished an in vivo model of beta(2)-adrenoceptor desensitization in guinea pig airways by administration of IL-1 beta intratracheally or chronic albut erol by inhalation. In the establishment of beta-adrenoceptor desensitizati on in response to both beta-agonist or inflammatory mediator, baseline pulm onary function responses were established to methacholine and isoproterenol -induced relaxation of methacholine bronchoconstriction. This was followed by the administration of IL-1 beta (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 d ays). After administration, the methacholine and isoproterenol-methacholine response was once again evaluated. Intratracheal administration of IL-1 be ta or chronic administration of albuterol significantly decreased (p < 0.05 ) the protective effect of isoproterenol on methacholine-induced bronchocon striction, eliciting beta-adrenoceptor desensitization in vivo. The in vivo model will be very useful in monitoring the effect of other potential drug s on beta-adrenoceptor function in the airways. (C) 1999 Elsevier Science I nc.