Cholinergic chemosensory cells in the trachea regulate breathing

Gabriela Krasteva, Brendan J Canning, Petra Hartmann, Tibor Z. Veres, Tamara Papadakis, Christian Mühlfeld, Kirstin Schliecker, Yvonne N. Tallini, Armin Braun, Holger Hackstein, Nelli Baal, Eberhard Weihe, Burkhard Schütz, Michael Kotlikoff, Ines Ibanez-Tallon, Wolfgang Kummer

Research output: Contribution to journalArticle

Abstract

In the epithelium of the lower airways, a cell type of unknown function has been termed "brush cell" because of a distinctive ultrastructural feature, an apical tuft of microvilli. Morphologically similar cells in the nose have been identified as solitary chemosensory cells responding to taste stimuli and triggering trigeminal reflexes. Here we show that brush cells of the mouse trachea express the receptors (Tas2R105, Tas2R108), the downstream signaling molecules (α-gustducin, phospholipase Cβ2) of bitter taste transduction, the synthesis and packaging machinery for acetylcholine, and are addressed by vagal sensory nerve fibers carrying nicotinic acetylcholine receptors. Tracheal application of an nAChR agonist caused a reduction in breathing frequency. Similarly, cycloheximide, a Tas2R108 agonist, evoked a drop in respiratory rate, being sensitive to nicotinic receptor blockade and epithelium removal. This identifies brush cells as cholinergic sensors of the chemical composition of the lower airway luminal microenvironment that are directly linked to the regulation of respiration.

Original languageEnglish (US)
Pages (from-to)9478-9483
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number23
DOIs
StatePublished - Jun 7 2011
Externally publishedYes

Fingerprint

Trachea
Cholinergic Agents
Respiration
Nicotinic Receptors
Epithelium
Phospholipases
Product Packaging
Cycloheximide
Respiratory Rate
Microvilli
Nerve Fibers
Nose
Acetylcholine
Reflex

Keywords

  • Airway sensory innervation
  • Bitter-tasting substances
  • Jugular-nodose ganglion
  • Respiratory epithelium

ASJC Scopus subject areas

  • General

Cite this

Cholinergic chemosensory cells in the trachea regulate breathing. / Krasteva, Gabriela; Canning, Brendan J; Hartmann, Petra; Veres, Tibor Z.; Papadakis, Tamara; Mühlfeld, Christian; Schliecker, Kirstin; Tallini, Yvonne N.; Braun, Armin; Hackstein, Holger; Baal, Nelli; Weihe, Eberhard; Schütz, Burkhard; Kotlikoff, Michael; Ibanez-Tallon, Ines; Kummer, Wolfgang.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 23, 07.06.2011, p. 9478-9483.

Research output: Contribution to journalArticle

Krasteva, G, Canning, BJ, Hartmann, P, Veres, TZ, Papadakis, T, Mühlfeld, C, Schliecker, K, Tallini, YN, Braun, A, Hackstein, H, Baal, N, Weihe, E, Schütz, B, Kotlikoff, M, Ibanez-Tallon, I & Kummer, W 2011, 'Cholinergic chemosensory cells in the trachea regulate breathing', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 23, pp. 9478-9483. https://doi.org/10.1073/pnas.1019418108
Krasteva, Gabriela ; Canning, Brendan J ; Hartmann, Petra ; Veres, Tibor Z. ; Papadakis, Tamara ; Mühlfeld, Christian ; Schliecker, Kirstin ; Tallini, Yvonne N. ; Braun, Armin ; Hackstein, Holger ; Baal, Nelli ; Weihe, Eberhard ; Schütz, Burkhard ; Kotlikoff, Michael ; Ibanez-Tallon, Ines ; Kummer, Wolfgang. / Cholinergic chemosensory cells in the trachea regulate breathing. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 23. pp. 9478-9483.
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