Effects of inflammation and acute beta-agonist inhalation on [beta]2ar signaling in human airways. Penn, Raymond B., Joseph R. Shaver, James G. Zangrilli, James E. Fish, Stephen P. Peters, and Jeffrey L. Benovic. Department of Pharmacology, Jefferson Cancer Institute, and Department of Medicine, Division of Pulmonary Medicine and Critical Care, Jefferson Medical College, Philadelphia, PA
APStracts 3:0098L, 1996.
Although alterations in [beta]2AR responsiveness may in part explain reports linking asthmatics treated with beta-agonists with deterioration of asthma control, few data exist examining b2AR regulation in human airway cells. We have employed a bronchoscopy model to examine inflammation- and beta-agonist-induced alterations in human bronchial epithelial cell [beta]2AR density and responsiveness. Allergic asthmatic subjects participated in two day protocols examining airways prior to and 24 h after segmental antigen challenge (SAC) with ragweed. To assess the effect of acute beta -agonist exposure, bronchoscopies were performed both with (+[beta] -Ag) and without (-[beta]-Ag) inhalation of beta-agonist 30 min prior to the procedure. Measurements of inflammatory cell infiltration were obtained by analysis of bronchoalveolar lavage (BAL) fluid, and [beta]2AR density and responsiveness were examined in bronchial epithelial cells obtained by bronchoscopic brushing. Neither SAC nor acute beta-agonist administration alone significantly affected epithelial cell [beta]2AR density. Beta-agonist-stimulated cAMP generation was significantly lower in the +[beta]-Ag groups compared to the -[beta]-Ag group, demonstrating acute agonist-specific [beta]2AR desensitization in vivo. SAC caused a small, statistically insignificant reduction in beta-agonist-stimulated cAMP production in both -[beta]-Ag or +[beta]-Ag groups. These data suggest that acute beta-agonist inhalation, but not airway inflammation, significantly reduces maximal [beta]2AR responsiveness in airway cells. 

Received 1 February 1996; accepted in final form 23 May 1996.
APS Manuscript Number L36-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96