Abstract
For a long time it was believed that β2-adrenergic receptor agonists used in the treatment of obstructive airway diseases worked primarily on airway smooth muscle cells, causing relaxation, whereas glucocorticoids primarily improved airway function via their anti-inflammatory action, indicating that their clinical synergism occurred at the organism rather than the cellular level. However, it is now becoming clear that both drug classes can affect airway function at multiple levels, including an integrated effect on several cell types. This article summarizes data on the molecular interaction between the two receptor systems, particularly with relevance to phenomena of β2-adrenergic receptor desensitization and glucocorticoid insensitivity in the airways. These molecular interactions may contribute to the observed clinical synergism between both drug classes in the treatment of obstructive airway diseases.
Footnotes
Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
doi:10.1124/mol.111.075481.
Please see the related article on page 1128.
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ABBREVIATIONS:
- B2AR
- β2-adrenergic receptor
- LABA
- long-acting B2AR agonist
- MAPK
- mitogen-activated protein kinase
- MKP-1
- mitogen-activated protein kinase phosphatase-1
- C/EBPα
- CCAAT/enhancer binding protein α
- NF-κB
- nuclear factor-κB.
- Received September 2, 2011.
- Accepted September 13, 2011.
- Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
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