An in vivo model of beta-adrenoceptor desensitization

B. T.Y. Chong, Devendra K. Agrawal, F. A. Romero, R. G. Townley

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Chronic use of β2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of β-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo model of β2-adrenoceptor desensitization in guinea pig airways by administration of IL-1β intratracheally or chronic albuterol by inhalation. In the establishment of β-adrenoceptor desensitization in response to both β-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-1β (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-1β or chronic administration of albuterol significantly decreased (p <0.05) the protective effect of isoproterenol on methacholine-induced bronchoconstriction, eliciting β-adrenoceptor desensitization in vivo. The in vivo model will be very useful in monitoring the effect of other potential drugs on β-adrenoceptor function in the airways. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)109-115
Number of pages7
JournalJournal of Pharmacological and Toxicological Methods
Volume40
Issue number2
DOIs
StatePublished - Dec 1 1998

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this