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.
Chong
B T
BT
Allergic Disease Center, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Agrawal
D K
DK
Romero
F A
FA
Townley
R G
RG
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001249:Asthma; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007375:Interleukin-1 / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000517:prevention & control*
D000318:Adrenergic beta-Agonists; D016085:Bronchoconstrictor Agents; D007375:Interleukin-1; D016210:Methacholine Chloride; D007545:Isoproterenol; D000420:Albuterol