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Inhibition of airway surface fluid absorption by cholinergic stimulation.
- Source :
-
Scientific reports [Sci Rep] 2016 Feb 05; Vol. 6, pp. 20735. Date of Electronic Publication: 2016 Feb 05. - Publication Year :
- 2016
-
Abstract
- In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20-70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways.
- Subjects :
- Amiloride analogs & derivatives
Amiloride pharmacology
Animals
Cells, Cultured
Ferrets
Humans
Rabbits
Respiratory Mucosa drug effects
Respiratory Mucosa metabolism
Sheep
Swine
Trachea cytology
Trachea metabolism
Atropine metabolism
Carbachol pharmacology
Epithelial Sodium Channels metabolism
Mucus metabolism
Trachea drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26846701
- Full Text :
- https://doi.org/10.1038/srep20735