Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1 , TRPV4

Title: Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung.

Authors: Matthew Baxter, Suffwan Eltom, Bilel Dekkak, Liang Yew-Booth, Eric D Dubuis, Sarah A Maher, Maria G Belvisi, Mark A Birrell

Journal, date & volume: Thorax, 2014 Dec , 69, 1080-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25301060

Abstract
COPD is an inflammatory disease usually associated with cigarette smoking (CS) with an increasing global prevalence and no effective medication. Extracellular ATP is increased in the COPD affected lung and may play a key role in driving CS-induced airway inflammation, but the mechanism involved in ATP release has eluded researchers. Recently, the transient receptor potential (TRP) and pannexin-1 channels have been suggested to play a role in other experimental paradigms. Thus, the aim of this work is to investigate if these channels are involved in CS-induced ATP release in the lung.Primary human cells were exposed to CS and extracellular ATP levels measured. Mice were exposed to mainstream CS and airway inflammation assessed. TRPV1/4 mRNA expression was assessed in human lung parenchyma.CS exposure caused a dose-related increase in ATP from primary airway bronchial epithelial cells. This was attenuated by blockers of TRPV1, TRPV4 and pannexin-1 channels. Parallel data was obtained using murine acute CS-driven model systems. Finally, TRPV1/4 mRNA expression was increased in lung tissue samples from patients with COPD.Extracellular ATP is increased in the COPD affected lung and may play a key role in driving disease pathophysiology. These experiments uncover a novel mechanism which may be responsible for CS-induced ATP release. These findings highlight novel targets that could lead to the development of medicine to treat this devastating disease.