Chronic exposure to a β2-adrenoceptor agonist increases the airway response to methacholine

Paula A. Witt-Enderby, Henry I. Yamamura, Marilyn Halonen, John D. Palmer, John W Bloom

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Scheduled chronic administration of β2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (β2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 ± 0.11 g vs. treated group = 1.50 ± 0.13 g, P < 0.05). The potency (EC75) was also increased in the albuterol-treated group. The potency for the control group was 5.6 μM (95% confidence limit: 2.3-13 μM) and was 1.7 μM (95% confidence limit: 1.1-2.8 μM, P < 0.05) for the albuterol-treated group. In a subgroup of animals, maximum contraction to KCl, a receptor-independent contractile stimulus, was not significantly different between the groups (control group = 0.79 ± 0.23 g vs. treated group = 0.82 ± 0.20 g). The potency (EC50) for KCl-induced contractions was also not significantly different between the groups: control = 12 mM (95% confidence limit: 3.3-44 mM) vs. treated 19 mM (95% confidence limit: 18-20 mM). These data demonstrate that chronic in vivo exposure to a β2-adrenoceptor agonist can alter the in vitro tissue bath response of airway smooth muscle to methacholine. Therefore, cholinergic mechanisms in the airway smooth muscle appear to be altered by chronic β2-adrenoceptor agonist exposure. This change in the airway smooth muscle response to methacholine may play a role in the increase of bronchial responsiveness associated with regular β2-adrenoceptor agonist use.

Original languageEnglish (US)
Pages (from-to)121-123
Number of pages3
JournalEuropean Journal of Pharmacology
Volume241
Issue number1
DOIs
Publication statusPublished - Sep 7 1993

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Keywords

  • (Rabbit)
  • Albuterol
  • Asthma
  • Methacholine
  • β-Adrenoceptor agonists

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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