{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:55:16Z","timestamp":1793278516842,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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 \u201ctaste\u201d substances are most probably initiated by tracheal brush cells (BC). Our single\u2010cell RNA\u2010seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (\n                    <jats:italic>Tas2r108<\/jats:italic>\n                    ,\n                    <jats:italic>Gnat3<\/jats:italic>\n                    ,\n                    <jats:italic>Trpm5<\/jats:italic>\n                    ). 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 [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in BC and subsequent ACh\u2010release. ACh\u2010release is regulated in an autocrine manner. While the muscarinic ACh\u2010receptors M3R and M1R are activating, M2R is inhibitory. Paracrine effects of ACh released in response to denatonium included increased [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in ciliated cells. Stimulation by denatonium or with\n                    <jats:italic>Pseudomonas<\/jats:italic>\n                    quinolone signaling molecules led to an increase in mucociliary clearance in explanted tracheae that was Trpm5\u2010 and M3R\u2010mediated. We show that ACh\u2010release 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.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901314rr","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T08:11:01Z","timestamp":1574410261000},"page":"316-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling"],"prefix":"10.1096","volume":"34","author":[{"given":"Monika I.","family":"Hollenhorst","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology Saarland University Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Innokentij","family":"Jurastow","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University of Giessen Giessen Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine (CS) University Hospital Charit\u00e9 Humboldt University of Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajender","family":"Nandigama","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Appenzeller","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Centre Mainfranken University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Core Unit SysMed University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Vogel","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for RNA\u2010based Infection Research (HIRI) Helmholtz\u2010Centre for Infection Research (HZI) W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Wiederhold","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology Justus\u2010Liebig\u2010University of Giessen Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Althaus","sequence":"additional","affiliation":[{"name":"School of Natural and Environmental Sciences Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Empting","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Optimization (DDOP) Helmholtz\u2010Institute for Pharmaceutical Research Saarland (HIPS)\u2010Helmholtz Centre for Infection Research (HZI) Saarbr\u00fccken Germany"},{"name":"Department of Pharmacy Saarland University Saarbr\u00fccken Germany"},{"name":"German Centre for Infection Research (DZIF) Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[{"name":"Cologne Centre for Genomics University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K. H.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Optimization (DDOP) Helmholtz\u2010Institute for Pharmaceutical Research Saarland (HIPS)\u2010Helmholtz Centre for Infection Research (HZI) Saarbr\u00fccken Germany"},{"name":"Department of Pharmacy Saarland University Saarbr\u00fccken Germany"},{"name":"German Centre for Infection Research (DZIF) Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Flockerzi","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology\/PZMS Saarland University Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan J.","family":"Canning","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Allergy and Clinical Immunology School of Medicine Johns Hopkins University Baltimore MD 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