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Pannexin 1 contributes to ATP release in airway epithelia.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2009 Nov; Vol. 41 (5), pp. 525-34. Date of Electronic Publication: 2009 Feb 12. - Publication Year :
- 2009
-
Abstract
- ATP is a paracrine regulator of critical airway epithelial cell functions, but the mechanism of its release is poorly understood. Pannexin (Panx) proteins, related to invertebrate innexins, form channels (called pannexons) that are able to release ATP from several cell types. Thus, ATP release via pannexons was examined in airway epithelial cells. Quantitative RT-PCR showed Panx1 expression in normal human airway epithelial cells during redifferentiation at the air-liquid interface (ALI), at a level comparable to that of alveolar macrophages; Panx3 was not expressed. Immunohistochemistry showed Panx1 expression at the apical pole of airway epithelia. ALI cultures exposed to hypotonic stress released ATP to an estimated maximum of 255 (+/-64) nM within 1 minute after challenge (n = 6 cultures from three different lungs) or to approximately 1.5 (+/-0.4) microM, recalculated to a normal airway surface liquid volume. Using date- and culture-matched cells (each n > or = 16 from 4 different lungs), the pannexon inhibitors carbenoxolone (10 microM) and probenecid (1 mM), but not the connexon inhibitor flufenamic acid (100 microM), inhibited ATP release by approximately 60%. The drugs affected Panx1 currents in Xenopus oocytes expressing exogenous Panx1 correspondingly. In addition, suppression of Panx1 expression using lentivirus-mediated production of shRNA in differentiated airway epithelial cells inhibited ATP release upon hypotonic stress by approximately 60% as well. These data not only show that Panx1 is expressed apically in differentiated airway epithelial cells but also that it contributes to ATP release in these cells.
- Subjects :
- Animals
Carbenoxolone pharmacology
Cell Dedifferentiation
Cells, Cultured
Connexins antagonists & inhibitors
Connexins genetics
Epithelial Cells drug effects
Flufenamic Acid pharmacology
Gene Expression Regulation
Humans
Hypotonic Solutions
Macrophages, Alveolar metabolism
Mice
Nerve Tissue Proteins antagonists & inhibitors
Nerve Tissue Proteins genetics
Osmotic Pressure
Probenecid pharmacology
RNA Interference
RNA, Messenger metabolism
Respiratory Mucosa drug effects
Stress, Physiological
Time Factors
Transfection
Xenopus
Adenosine Triphosphate metabolism
Connexins metabolism
Epithelial Cells metabolism
Mucociliary Clearance
Nerve Tissue Proteins metabolism
Paracrine Communication
Respiratory Mucosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4989
- Volume :
- 41
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 19213873
- Full Text :
- https://doi.org/10.1165/rcmb.2008-0367OC