Par-2-Activated Secretion By Airway Gland Serous Cells: Role For Cftr And Inhibition By Pseudomonas Aeruginosa

Airway submucosal gland serous cells are important sites of fluid secretion in conducting airways. Serous cells also express the cystic fibrosis (CF) transmembrane conductance regulator (CFTR). Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor that activates secretion from intact airway glands. We tested if and how human nasal serous cells secrete fluid in response to PAR-2 stimulation using Ca2+ imaging and simultaneous differential interference contrast imaging to track isosmotic cell shrinking and swelling reflecting activation of solute efflux and influx pathways, respectively. During stimulation of PAR-2, serous cells exhibited dose-dependent increases in intracellular Ca2+. At stimulation levels >EC50 for Ca2+, serous cells simultaneously shrank similar to 20% over similar to 90s due to KCI efflux reflecting Ca2+-activated CI- channel (CaCC, likely TMEM16A)-dependent secretion. At lower levels of PAR-2 stimulation (More