title: Regulation of epithelial sodium channel α-subunit expression by adenosine receptor A₂a in alveolar epithelial cells.
abstract: BACKGROUND
  The amiloride-sensitive epithelial sodium channel α-subunit (α-ENaC) is an important factor for alveolar fluid clearance during acute lung injury. The relationship between adenosine receptor A(2a) (A(2a)AR) expressed in alveolar epithelial cells and α-ENaC is poorly understood. We targeted the A(2a)AR in this study to investigate its role in the expression of α-ENaC and in acute lung injury.
  
  
  METHODS
  A549 cells were incubated with different concentrations of A(2a)AR agonist CGS-21680 and with 100 µmol/L CGS-21680 for various times. Rats were treated with lipopolysaccharide (LPS) after CGS-21680 was injected. Animals were sacrificed and tissue was harvested for evaluation of lung injury by analysis of the lung wet-to-dry weight ratio, lung permeability and myeloperoxidase activity. RT-PCR and Western blotting were used to determine the mRNA and protein expression levels of α-ENaC in A549 cells and alveolar type II epithelial cells.
  
  
  RESULTS
  Both mRNA and protein levels of α-ENaC were markedly higher from 4 hours to 24 hours after exposure to 100 µmol/L CGS-21680. There were significant changes from 0.1 µmol/L to 100 µmol/L CGS-21680, with a positive correlation between increased concentrations of CGS-21680 and expression of α-ENaC. Treatment with CGS-21680 during LPS induced lung injury protected the lung and promoted α-ENaC expression in the alveolar epithelial cells.
  
  
  CONCLUSIONS
  Activation of A(2a)AR has a protective effect during the lung injury, which may be beneficial to the prognosis of acute lung injury.
authors: Department of Respiratory Diseases, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors: Wang
authors: W
authors: Deng
authors: Dao-Xin
authors: DX
authors: Wang
authors: Wei
authors: W
authors: Zhang
authors: Chang-Yi
authors: CY
authors: Li
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053503:Epithelial Sodium Channels; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine