Protease-activated receptor 2 mediates mucus secretion in the airway submucosal gland.
Protease-activated receptor 2 (PAR2), a G protein-coupled receptor expressed in airway epithelia and smooth muscle, plays an important role in airway inflammation. In this study, we demonstrated that activation of PAR2 induces mucus secretion from the human airway gland and examined the underlying mechanism using the porcine and murine airway glands. The mucosa with underlying submucosal glands were dissected from the cartilage of tissues, pinned with the mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of the bubble diameter. The Ca(2+)-sensitive dye Fura2-AM was used to determine intracellular Ca(2+) concentration ([Ca(2+)](i)) by means of spectrofluorometry. Stimulation of human tracheal mucosa with PAR2-activating peptide (PAR2-AP) elevated intracellular Ca(2+) and induced glandular secretion equal to approximately 30% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, and this response was dependent on Ca(2+) and anion secretion. When the mouse trachea were exposed to PAR2-AP, large amounts of secretion were observed in both wild type and ΔF508 cystic fibrosis transmembrane conductance regulator mutant mice but there is no secretion from PAR-2 knock out mice. In conclusion, PAR2-AP is an agonist for mucus secretion from the airway gland that is Ca(2+)-dependent and cystic fibrosis transmembrane conductance regulator-independent.
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Hyun Jae
HJ
Lee
Yu-Mi
YM
Yang
Kyubo
K
Kim
Dong Min
DM
Shin
Joo-Heon
JH
Yoon
Hyung-Ju
HJ
Cho
Jae Young
JY
Choi
D000328:Adult; D000368:Aged; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism*; D009113:Muramidase / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*
C487404:2-furoyl-LIGRLO-amide; D009842:Oligopeptides; D044464:Receptor, PAR-2; D009113:Muramidase; D002118:Calcium