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http://purl.uniprot.org/citations/32959891http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32959891http://www.w3.org/2000/01/rdf-schema#comment"

Background and purpose

Mucociliary clearance is an innate immune process of the airways, essential for removal of respiratory pathogens. It depends on ciliary beat and ion and fluid homeostasis of the epithelium. We have shown that nicotinic ACh receptors (nAChRs) activate ion transport in mouse tracheal epithelium. Yet the receptor subtypes and signalling pathways involved remained unknown.

Experimental approach

Transepithelial short circuit currents (ISC ) of freshly isolated mouse tracheae were recorded using the Ussing chamber technique. Changes in [Ca2+ ]i were studied on freshly dissociated mouse tracheal epithelial cells.

Key results

Apical application of the nAChR agonist nicotine transiently increased ISC . The nicotine effect was abolished by the nAChR antagonist mecamylamine. α-Bungarotoxin (α7 antagonist) had no effect. The agonists epibatidine (α3β2, α4β2, α4β4 and α3β4) and A-85380 (α4β2 and α3β4) increased ISC . The antagonists dihydro-β-erythroidine (α4β2, α3β2, α4β4 and α3β4), α-conotoxin MII (α3β2) and α-conotoxin PnIA (α3β2) reduced the nicotine effect. Nicotine- and epibatidine-induced currents were unaltered in β2-/- mice, but in β4-/- mice no increase was observed. In the presence of thapsigargin (endoplasmatic reticulum Ca2+ -ATPase inhibitor) or the ryanodine receptor antagonists JTV-519 and dantrolene there was a reduction in the nicotine-effect, indicating involvement of Ca2+ release from intracellular stores. Additionally, the PKA inhibitor H-89 and the TMEM16A (Ca2+ -activated chloride channel) inhibitor T16Ainh-A01 significantly reduced the nicotine-effect.

Conclusion and implications

α3β4 nAChRs are responsible for the nicotine-induced current changes via Ca2+ release from intracellular stores, PKA and ryanodine receptor activation. These nAChRs might be possible targets to stimulate chloride transport via TMEM16A."xsd:string
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http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/author"Kumar P."xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/author"Scholze P."xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/author"Krasteva-Christ G."xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/author"Fronius M."xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/author"Hollenhorst M.I."xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/name"Br J Pharmacol"xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/pages"5595-5608"xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/title"Nicotine stimulates ion transport via metabotropic beta4 subunit containing nicotinic ACh receptors."xsd:string
http://purl.uniprot.org/citations/32959891http://purl.uniprot.org/core/volume"177"xsd:string
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