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Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma.

Abstract
G protein-coupled receptors (GPCRs) utilize (at least) two signal transduction pathways to elicit cellular responses including the classic G protein-dependent, and the more recently discovered β-arrestin-dependent, signaling pathways. In human and murine models of asthma, agonist-activation of β2-adrenergic receptor (β2AR) or Protease-activated-receptor-2 (PAR2) results in relief from bronchospasm via airway smooth muscle relaxation. However, chronic activation of these receptors, leads to pro-inflammatory responses. One plausible explanation underlying the paradoxical effects of β2AR and PAR2 agonism in asthma is that the beneficial and harmful effects are associated with distinct signaling pathways. Specifically, G protein-dependent signaling mediates relaxation of airway smooth muscle, whereas β-arrestin-dependent signaling promotes inflammation. This review explores the evidence supporting the hypothesis that β-arrestin-dependent signaling downstream of β2AR and PAR2 is detrimental in asthma and examines the therapeutic opportunities for selectively targeting this pathway.
AuthorsJulia K L Walker, Katherine A DeFea
JournalCurrent opinion in pharmacology (Curr Opin Pharmacol) Vol. 16 Pg. 142-7 (Jun 2014) ISSN: 1471-4973 [Electronic] England
PMID24907413 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Arrestins
  • Receptor, PAR-2
  • Receptors, Adrenergic, beta-2
  • beta-Arrestins
Topics
  • Animals
  • Arrestins (metabolism)
  • Asthma (metabolism)
  • Humans
  • Receptor, PAR-2 (metabolism)
  • Receptors, Adrenergic, beta-2 (metabolism)
  • beta-Arrestins

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