Effects of inflammation and acute beta-agonist inhalation on beta 2-AR signaling in human airways.
Publication/Presentation Date
10-1-1996
Abstract
Although alterations in beta 2-adrenergic receptor (AR) responsiveness may in part explain reports linking deterioration of asthma control with beta-agonist treatment of asthmatics, few data exist on beta 2-AR 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 2-AR density and responsiveness. Allergic asthmatic subjects participated in 2-day protocols examining airways before 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 before the procedure. Measurements of inflammatory cell infiltration were obtained by analysis of bronchoalveolar lavage fluid, and beta 2-AR 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 2-AR density. beta-Agonist-stimulated adenosine 3', 5'-cyclic monophosphate (cAMP) generation was significantly lower in the + beta-Ag groups compared with the-beta-Ag group, demonstrating acute agonist-specific beta 2-AR 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 lata suggest that acute beta-agonist inhalation, but not airway inflammation, significantly reduces maximal beta 2-AR responsiveness in airway cells.
Volume
271
Issue
4 Pt 1
First Page
601
Last Page
608
ISSN
0002-9513
Published In/Presented At
Penn, R. B., Shaver, J. R., Zangrilli, J. G., Pollice, M., Fish, J. E., Peters, S. P., & Benovic, J. L. (1996). Effects of inflammation and acute beta-agonist inhalation on beta 2-AR signaling in human airways. The American journal of physiology, 271(4 Pt 1), L601–L608. https://doi.org/10.1152/ajplung.1996.271.4.L601
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
8897908
Department(s)
Administration and Leadership
Document Type
Article