Format

Send to

Choose Destination
Int Immunopharmacol. 2015 Nov;29(1):166-72. doi: 10.1016/j.intimp.2015.08.010. Epub 2015 Aug 15.

Luminal acetylcholine does not affect the activity of the CFTR in tracheal epithelia of pigs.

Author information

1
Institute of Animal Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26, 35392 Giessen, Germany.
2
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, German Center for Lung Research (DZL), Aulweg 123, 35385 Giessen, Germany.
3
Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054, New Zealand. Electronic address: martin.fronius@otago.ac.nz.

Abstract

Fluid homeostasis mediated by the airway epithelium is required for proper lung function, and the CFTR (cystic fibrosis transmembrane conductance regulator) Cl(-) channel is crucial for these processes. Luminal acetylcholine (ACh) acts as an auto-/paracrine mediator to activate Cl(-) channels in airway epithelia and evidence exists showing that nicotinic ACh receptors activate CFTR in murine airway epithelia. The present study investigated whether or not luminal ACh regulates CFTR activity in airway epithelia of pigs, an emerging model for investigations of human airway disease and cystic fibrosis (CF) in particular. Transepithelial ion currents of freshly dissected pig tracheal preparations were measured with Ussing chambers. Application of luminal ACh (100 μM) induced an increase of the short-circuit current (I(SC)). The ACh effect was mimicked by muscarine and pilocarpine (100 μM each) and was sensitive to muscarinic receptor antagonists (atropine, 4-DAMP, pirenzepine). No changes of the I(SC) were observed by nicotine (100 μM) and ACh responses were not affected by nicotine or mecamylamine (25 μM). Luminal application of IBMX (I, 100 μM) and forskolin (F, 10 μM), increase the I(SC) and the I/F-induced current were decreased by the CFTR inhibitor GlyH-101 (GlyH, 50 μM) indicating increased CFTR activity by I/F. In contrast, GlyH did not affect the ACh-induced current, indicating that the ACh response does not involve the activation of the CFTR. Results from this study suggest that luminal ACh does not regulate the activity of the CFTR in tracheal epithelia of pigs which opposes observation from studies using mice airway epithelium.

KEYWORDS:

CFTR; Cl(−) secretion; Non-neuronal acetylcholine; Pig; Tracheal epithelium; Transepithelial ion transport

PMID:
26286842
DOI:
10.1016/j.intimp.2015.08.010
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center