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Cholinergic chemosensory cells in the trachea regulate breathing

: Krasteva, G.; Canning, B.J.; Hartmann, P.; Veres, T.Z.; Papadakis, T.; Mühlfeld, C.; Schliecker, K.; Tallini, Y.N.; Braun, A.; Hackstein, H.; Baal, N.; Weihe, E.; Schütz, B.; Kotlikoff, M.; Ibanez-Tallon, I.; Kummer, W.

Fulltext urn:nbn:de:0011-n-1898317 (984 KByte PDF)
MD5 Fingerprint: d7b29ee7e224da1c9635ea190ef033e6
Created on: 11.1.2012

Proceedings of the National Academy of Sciences of the United States of America : PNAS 108 (2011), No.23, pp.9478-9483
ISSN: 0027-8424
ISSN: 1091-6490
Journal Article, Electronic Publication
Fraunhofer ITEM ()
chemoreceptor cells; Choline O-Acetyltransferase; green fluorescent protein; heterotrimeric GTP-Binding proteins; reverse transcriptase polymerase chain reaction; vesicular acetylcholine transport proteins; phospholipase C beta; microvilli; flow cytometry; immunohistochemistry; mouse; microscopy; taste; Trachea; Receptors

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 (-gustducin, phospholipase C2) 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 co mposition of the lower airway luminal microenvironment that are directly linked to the regulation of respiration.