TY - JOUR
T1 - Local regulation of cystic fibrosis transmembrane regulator and epithelial sodium channel in airway epithelium.
AU - Huang, Pingbo
AU - Gilmore, Elaine
AU - Kultgen, Patricia
AU - Barnes, Paul
AU - Milgram, Sharon
AU - Stutts, M. Jackson
PY - 2004
Y1 - 2004
N2 - Regulation of cystic fibrosis transmembrane regulator (CFTR) and epithelial sodium channel (ENaC) in airway epithelia strongly influences the rate of mucociliary clearance (MCC) by determining the volume of airway surface liquid. MCC increases in response to stimuli originating on the airway surface, and CFTR and ENaC in airway epithelia appear to be regulated by local rather than systemic signaling. Although all signals that regulate CFTR and ENaC in airways have not been identified, the release of nucleotides from airway epithelial cells exposed to physical stimuli initiates a series of events that coordinately favor increased MCC. These events include activation of adenosine A2B receptors that stimulate CFTR and P2Y2 receptors that inhibit ENaC. Together these actions result in an increased volume of airway surface liquid and increased MCC rates. Stimulation of CFTR by A(2B)AR uses protein kinase (PK) A signaling elements that are localized within the apical/subapical compartment, including G proteins, adenylyl cyclase, PKA-II, A-kinase anchoring proteins, and phosphodiesterases. Inhibition of ENaC by P2Y2 receptors appears to be mediated by phospholipase C-beta3, possibly through an effect on the levels of phosphatidylinositol 4,5-bisphosphonate in the apical membrane.
AB - Regulation of cystic fibrosis transmembrane regulator (CFTR) and epithelial sodium channel (ENaC) in airway epithelia strongly influences the rate of mucociliary clearance (MCC) by determining the volume of airway surface liquid. MCC increases in response to stimuli originating on the airway surface, and CFTR and ENaC in airway epithelia appear to be regulated by local rather than systemic signaling. Although all signals that regulate CFTR and ENaC in airways have not been identified, the release of nucleotides from airway epithelial cells exposed to physical stimuli initiates a series of events that coordinately favor increased MCC. These events include activation of adenosine A2B receptors that stimulate CFTR and P2Y2 receptors that inhibit ENaC. Together these actions result in an increased volume of airway surface liquid and increased MCC rates. Stimulation of CFTR by A(2B)AR uses protein kinase (PK) A signaling elements that are localized within the apical/subapical compartment, including G proteins, adenylyl cyclase, PKA-II, A-kinase anchoring proteins, and phosphodiesterases. Inhibition of ENaC by P2Y2 receptors appears to be mediated by phospholipase C-beta3, possibly through an effect on the levels of phosphatidylinositol 4,5-bisphosphonate in the apical membrane.
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U2 - 10.1513/pats.2306012
DO - 10.1513/pats.2306012
M3 - Review article
C2 - 16113409
AN - SCOPUS:24944495525
SN - 1546-3222
VL - 1
SP - 33
EP - 37
JO - Proceedings of the American Thoracic Society
JF - Proceedings of the American Thoracic Society
IS - 1
ER -