Modulation of epithelial sodium channel activity by lipopolysaccharide in alveolar type II cells: involvement of purinergic signaling

Autor: Valerie Tardif, Erik Gendreau-Berthiaume, Marie-Claude Tessier, Frédéric Morneau, Yves Berthiaume, André Dagenais, Ryszard Grygorczyk, Jacynthe Lavoie, Émilie Boncoeur
Rok vydání: 2010
Předmět:
Lipopolysaccharides
Male
Pulmonary and Respiratory Medicine
Epithelial sodium channel
medicine.medical_specialty
Time Factors
Lipopolysaccharide
Physiology
Intracellular Space
Suramin
Biology
medicine.disease_cause
Models
Biological
Cystic fibrosis
Amiloride
Rats
Sprague-Dawley
chemistry.chemical_compound
Adenosine Triphosphate
Physiology (medical)
Internal medicine
medicine
Animals
Trypsin
Epithelial Sodium Channels
Receptor
Protein Kinase C
Protein kinase C
urogenital system
Pseudomonas aeruginosa
Cell Membrane
Sodium
Receptors
Purinergic
Biological Transport
Cell Biology
respiratory system
Purinergic signalling
medicine.disease
Molecular biology
Rats
Protein Subunits
Endocrinology
chemistry
Alveolar Epithelial Cells
Type C Phospholipases
Signal transduction
Ion Channel Gating
Signal Transduction
Zdroj: American Journal of Physiology-Lung Cellular and Molecular Physiology. 298:L417-L426
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.00170.2009
Popis: Pseudomonas aeruginosa is a gram-negative bacterium that causes chronic infection in cystic fibrosis patients. We reported recently that P. aeruginosa modulates epithelial Na+ channel (ENaC) expression in experimental chronic pneumonia models. For this reason, we tested whether LPS from P. aeruginosa alters ENaC expression and activity in alveolar epithelial cells. We found that LPS induces a ∼60% decrease of ENaC apical current without significant changes in intracellular ENaC or surface protein expression. Because a growing body of evidence reports a key role for extracellular nucleotides in regulation of ion channels, we evaluated the possibility that modulation of ENaC activity by LPS involves extracellular ATP signaling. We found that alveolar epithelial cells release ATP upon LPS stimulation and that pretreatment with suramin, a P2Y2 purinergic receptor antagonist, inhibited the effect of LPS on ENaC. Furthermore, ET-18-OCH3, a PLC inhibitor, and Go-6976, a PKC inhibitor, were able to partially prevent ENaC inhibition by LPS, suggesting that the actions of LPS on ENaC current were mediated, in part, by the PKC and PLC pathways. Together, these findings demonstrate an important role of extracellular ATP signaling in the response of epithelial cells to LPS.
Databáze: OpenAIRE
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