title: Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Baxter
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Suffwan
authors.initials: S
authors.lastname: Eltom
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Bilel
authors.initials: B
authors.lastname: Dekkak
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Liang
authors.initials: L
authors.lastname: Yew-Booth
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Dubuis
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Maher
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Belvisi
authors.affiliation: Respiratory Pharmacology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birrell
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D002478:Cells, Cultured; D017630:Connexins / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D058486:Receptors, Purinergic P2X7 / Q000502:physiology; D020545:Respiratory Mucosa / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D050916:TRPV Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D017630:Connexins; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; D012333:RNA, Messenger; D058486:Receptors, Purinergic P2X7; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C416986:TRPV4 protein, human; D014028:Tobacco Smoke Pollution; D000255:Adenosine Triphosphate
keywords: COPD Pathology; COPD Pharmacology