Item Type: | Article |
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Title: | Cholinergic chemosensory cells in the trachea regulate breathing |
Creators Name: | Krasteva, G., Canning, B.J., Hartmann, P., Veres, T.Z., Papadakis, T., Muehlfeld, C., Schliecker, K., Tallini, Y.N., Braun, A., Hackstein, H., Baal, N., Weihe, E., Schuetz, B., Kotlikoff, M., 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 |
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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