Marked increases in mucociliary clearance produced by synergistic secretory agonists or inhibition of the epithelial sodium channel
- Title
- Marked increases in mucociliary clearance produced by synergistic secretory agonists or inhibition of the epithelial sodium channel
- Author
- 정진혁
- Keywords
- CILIARY BEAT FREQUENCY; VASOACTIVE-INTESTINAL-PEPTIDE; TRACHEAL SUBMUCOSAL GLANDS; FIBROSIS AIRWAY EPITHELIA; CYSTIC-FIBROSIS; MUCUS SECRETION; BICARBONATE SECRETION; PULMONARY-DISEASE; FERRET TRACHEA; LUNG-DISEASE
- Issue Date
- 2016-11
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v. 6, NO 36806, Page. 1-12
- Abstract
- Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca2+-activated chloride channels mediate anion/fluid secretion. MCCV was increased by the cAMP-elevating agonists, forskolin or isoproterenol (10 mu M) and by the Ca2+-elevating agonist, carbachol (0.3 mu M). The CFTR-selective inhibitor, CFTRinh-172, modestly reduced MCCV-increases induced by forskolin or isoproterenol but not increases induced by carbachol. The ENaC inhibitor benzamil increased basal MCCV as well as MCCV increases produced by forskolin or carbachol. MCC velocity was most dramatically accelerated by the synergistic combination of forskolin and carbachol, which produced near-maximal clearance rates regardless of prior treatment with CFTR or ENaC inhibitors. In CF airways, where CFTR-mediated secretion (and possibly synergistic MCC) is lost, ENaC inhibition via exogenous agents may provide therapeutic benefit, as has long been proposed.
- URI
- https://www.nature.com/articles/srep36806https://repository.hanyang.ac.kr/handle/20.500.11754/101090
- ISSN
- 2045-2322
- DOI
- 10.1038/srep36806
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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