GPCRs and arrestins in airways: implications for asthma.

Abstract

The obstructive lung disease asthma is treated by drugs that target, either directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq are the primary mediators of airway smooth muscle (ASM) contraction and increased airway resistance, whereas the Gs-coupled beta-2-adrenoceptor (β2AR) promotes pro-relaxant signaling in and relaxation of ASM resulting in greater airway patency and reversal of life-threatening bronchoconstriction. In addition, GPCR-mediated functions in other cell types, including airway epithelium and hematopoietic cells, are involved in the control of lung inflammation that causes most asthma. The capacity of arrestins to regulate GPCR signaling, via either control of GPCR desensitization/resensitization or G protein-independent signaling, renders arrestins an intriguing therapeutic target for asthma and other obstructive lung diseases. This review will focus on the potential role of arrestins in those GPCR-mediated airway cell functions that are dysregulated in asthma.

• Authors: Raymond B Penn, Richard A Bond, Julia K L Walker
• Journal: Handbook of experimental pharmacology (Handb Exp Pharmacol) Vol. 219 Pg. 387-403 ( 2014) ISSN: 0171-2004 [Print] Germany
• PMID: 24292841 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Asthmatic Agents
• Arrestins
• Receptors, G-Protein-Coupled

Topics

• Airway Resistance (physiology)
• Animals
• Anti-Asthmatic Agents (pharmacology)
• Arrestins (metabolism)
• Asthma (drug therapy, physiopathology)
• Humans
• Inflammation (drug therapy, physiopathology)
• Molecular Targeted Therapy
• Muscle Contraction (physiology)
• Muscle, Smooth (metabolism)
• Receptors, G-Protein-Coupled (drug effects, metabolism)
• Signal Transduction (physiology)