Local regulation of cystic fibrosis transmembrane regulator and epithelial sodium channel in airway epithelium.
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.
Huang
Pingbo
P
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong. bohuangp@ust.hk
Gilmore
Elaine
E
Kultgen
Patricia
P
Barnes
Paul
P
Milgram
Sharon
S
Stutts
M Jackson
MJ
D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D053503:Epithelial Sodium Channels; D006801:Humans; D020545:Respiratory Mucosa / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism*
C505032:CFTR protein, human; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator