beta-Adrenoceptor inverse agonists in asthma.

Journal Article (Review;Journal Article)

Beta(2)-adrenoceptor (beta(2)-AR) agonists are very effective bronchodilators and play a major role in every stage of asthma management. However, their chronic, regular use is associated with detrimental effects including an increase in asthma-related deaths. Conversely, recent data suggest that certain beta-blockers, specifically beta-adrenoceptor (beta-AR) inverse agonists, may be useful in the chronic treatment of asthma. Here we review the data for this observation and the signaling pathways that may be involved. The data suggest that beta(2)-AR signaling is required to produce maximal airway inflammation and hyperresponsiveness, and the signaling pathway responsible for these effects is likely the non-canonical beta-arrestin-2 pathway. Therefore, beta-AR inverse agonists may produce their beneficial chronic effects by inhibiting constitutive or ligand-induced activation of this pathway. Both lung parenchymal and hematopoietic cells appear to be involved in mediating the beneficial effects of beta-AR inverse agonists.

Full Text

Duke Authors

Cited Authors

  • Dickey, BF; Walker, JKL; Hanania, NA; Bond, RA

Published Date

  • June 2010

Published In

Volume / Issue

  • 10 / 3

Start / End Page

  • 254 - 259

PubMed ID

  • 20399707

Pubmed Central ID

  • PMC2905467

Electronic International Standard Serial Number (EISSN)

  • 1471-4973

International Standard Serial Number (ISSN)

  • 1471-4892

Digital Object Identifier (DOI)

  • 10.1016/j.coph.2010.03.002


  • eng