Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle.

Journal Article (Academic article)

Chronic use of inhaled beta-agonists by asthmatics is associated with a loss of bronchoprotective effect and deterioration of asthma control. Beta-agonist-promoted desensitization of airway smooth muscle beta-2-adrenergic receptors, mediated by G protein-coupled receptor kinases and arrestins, is presumed to underlie these effects, but such a mechanism has never been demonstrated. Using in vitro, ex vivo, and in vivo murine models, we demonstrate that beta-arrestin-2 gene ablation augments beta-agonist-mediated airway smooth muscle relaxation, while augmenting beta-agonist-stimulated cyclic adenosine monophosphate production. In cultures of human airway smooth muscle, small interfering RNA-mediated knockdown of arrestins also augments beta-agonist-stimulated cyclic adenosine monophosphate production. Interestingly, signaling and function mediated by m2/m3 muscarinic acetylcholine receptors or prostaglandin E(2) receptors were not affected by either beta-arrestin-2 knockout or arrestin knockdown. Thus, arrestins are selective regulators of beta-2-adrenergic receptor signaling and function in airway smooth muscle. These results and our previous findings, which demonstrate a role for arrestins in the development of allergic inflammation in the lung, identify arrestins as potentially important therapeutic targets for obstructive airway diseases.

Full Text

Duke Authors

Cited Authors

  • Deshpande, DA; Theriot, BS; Penn, RB; Walker, JK

Published Date

  • July 2008

Published In

Volume / Issue

  • 22 / 7

Start / End Page

  • 2134 - 2141

PubMed ID

  • 18337459

Pubmed Central ID

  • PMC3514410

International Standard Serial Number (ISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.07-102459


  • English