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Titel: Acute nicotine administration stimulates ciliary activity via α3β4 nAChR in the mouse trachea
VerfasserIn: Perniss, Alexander
Latz, Ariane
Boseva, Ivelina
Papadakis, Tamara
Dames, Claudia
Meisel, Christian
Meisel, Andreas
Scholze, Petra
Kummer, Wolfgang
Krasteva-Christ, Gabriela
Sprache: Englisch
Titel: International Immunopharmacology
Bandnummer: 84
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2020
Freie Schlagwörter: Mucociliary clearance
Nicotine
nAChR
Non-neuronal acetylcholine
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Mucociliary clearance, the continuous removal of mucus-trapped particles by cilia-driven directed transport of the airway lining fluid, is the primary innate defense mechanism of the airways. It is potently activated by acetylcholine (ACh) addressing muscarinic receptors with a currently less defined role of nicotinic ACh receptors (nAChR). We here set out to determine their contribution in driving ciliary activity in an explanted mouse trachea preparation utilizing selected agonists and antagonists and nAChR-subunit deficient mice. Nicotine (100 µM) induced an increase in ciliary beat frequency, accompanied by a sharp, but not long lasting increase in particle transport speed (PTS) on the mucosal surface showing marked desensitization within the next 30 min. Nicotine-induced PTS acceleration was sensitive to the general nAChR inhibitors mecamylamine and d-tubocurarine as well as to the α3β4-nAChR antagonist α-conotoxin AulB, but not to other antagonists primarily addressing α3β2-nAChR or α4-, α7- and α9-containing nAChR. Agonists at α3β*-nAChR (epibatidine, cytisine), but not cotinine mimicked the effect. Tracheas from mice with genetic deletion of nAChR subunits α5, α7, α9, α10, α9/10, and β2 retained full PTS response to nicotine, whereas this was entirely lost in tracheas from mice lacking the β4-subunit. Collectively, our data show that nicotinic stimulation of α3β4-nAChR acutely increases PTS to the same extent as the established strong activator ATP. In view of the marked desensitization observed in the present setting, the physiological relevance of these receptors in adapting mucociliary clearance to rapidly changing endogenous or environmental stimuli remains open.
DOI der Erstveröffentlichung: 10.1016/j.intimp.2020.106496
URL der Erstveröffentlichung: https://doi.org/10.1016/j.intimp.2020.106496
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-422528
hdl:20.500.11880/37938
http://dx.doi.org/10.22028/D291-42252
ISSN: 1567-5769
Datum des Eintrags: 24-Jun-2024
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Anatomie und Zellbiologie
Professur: M - Prof. Dr. Gabriela Krasteva-Christ
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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