Please use this identifier to cite or link to this item: doi:10.22028/D291-33177
Title: Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling
Author(s): Hollenhorst, Monika I.
Jurastow, Innokentij
Nandigama, Rajender
Appenzeller, Silke
Li, Lei
Vogel, Jörg
Wiederhold, Stephanie
Althaus, Mike
Empting, Martin
Altmüller, Janine
Hirsch, Anna K. H.
Flockerzi, Veit
Canning, Brendan J.
Saliba, Antoine-Emmanuel
Krasteva-Christ, Gabriela
Language: English
Title: The FASEB Journal : the journal of the Federation of American Societies for Experimental Biology
Volume: 34
Issue: 1
Pages: 316-332
Publisher/Platform: Wiley
Year of Publication: 2019
Free key words: acetylcholine
brush cells
mucociliary clearance
single-cell RNA-seq
taste
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: For protection from inhaled pathogens many strategies have evolved in the airways such as mucociliary clearance and cough. We have previously shown that protective respiratory reflexes to locally released bacterial bitter "taste" substances are most probably initiated by tracheal brush cells (BC). Our single-cell RNA-seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (Tas2r108, Gnat3, Trpm5). We directly demonstrate the secretion of acetylcholine (ACh) from BC upon stimulation with the Tas2R agonist denatonium. Inhibition of the taste transduction cascade abolished the increase in [Ca2+]i in BC and subsequent ACh-release. ACh-release is regulated in an autocrine manner. While the muscarinic ACh-receptors M3R and M1R are activating, M2R is inhibitory. Paracrine effects of ACh released in response to denatonium included increased [Ca2+]i in ciliated cells. Stimulation by denatonium or with Pseudomonas quinolone signaling molecules led to an increase in mucociliary clearance in explanted tracheae that was Trpm5- and M3R-mediated. We show that ACh-release from BC via the bitter taste cascade leads to immediate paracrine protective responses that can be boosted in an autocrine manner. This mechanism represents the initial step for the activation of innate immune responses against pathogens in the airways.
DOI of the first publication: 10.1096/fj.201901314RR
Link to this record: urn:nbn:de:bsz:291--ds-331775
hdl:20.500.11880/30539
http://dx.doi.org/10.22028/D291-33177
ISSN: 1530-6860
0892-6638
Date of registration: 3-Feb-2021
Description of the related object: Supporting Information
Related object: https://faseb.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1096%2Ffj.201901314RR&file=fsb220054-sup-0001-FigS1-S6.pdf
https://faseb.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1096%2Ffj.201901314RR&file=fsb220054-sup-0002-TableS1.xls
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Anatomie und Zellbiologie
NT - Pharmazie
Professorship: M - Keiner Professur zugeordnet
NT - Prof. Dr. Anna Hirsch
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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