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Cholinergic chemosensory cells in the trachea regulate breathing

Item Type:Article
Title:Cholinergic chemosensory cells in the trachea regulate breathing
Creators Name:Krasteva, G. and Canning, B.J. and Hartmann, P. and Veres, T.Z. and Papadakis, T. and Muehlfeld, C. and Schliecker, K. and Tallini, Y.N. and Braun, A. and Hackstein, H. and Baal, N. and Weihe, E. and Schuetz, B. and Kotlikoff, M. and Ibanez-Tallon, I. and Kummer, W.
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 (alpha-gustducin, phospholipase C(beta2)) 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.
Keywords:Airway Sensory Innervation, Respiratory Epithelium, Jugular-Nodose Ganglion, Bitter-Tasting Substances, Chemoreceptor Cells, Choline O-Acetyltransferase, Confocal Microscopy, Electron Microscopy, Flow Cytometry, G-Protein-Coupled Receptors, Green Fluorescent Proteins, Heterotrimeric GTP-Binding Proteins, Immunohistochemistry, Microfilament Proteins, Microvilli, Nicotinic Receptors, Phospholipase C Beta, Respiration, Reverse Transcriptase Polymerase Chain Reaction, Taste, Trachea, Vesicular Acetylcholine Transport Proteins, Animals, Inbred C57BL Mice, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:108
Number:23
Page Range:9478-9483
Date:7 June 2011
Official Publication:https://doi.org/10.1073/pnas.1019418108
PubMed:View item in PubMed

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