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 C(β2)) 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chemoreceptor Cells / metabolism*
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Choline O-Acetyltransferase / genetics
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Choline O-Acetyltransferase / metabolism
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Female
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Flow Cytometry
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Heterotrimeric GTP-Binding Proteins / genetics
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Heterotrimeric GTP-Binding Proteins / metabolism
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Immunohistochemistry
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Male
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Mice
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Mice, Inbred C57BL
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Microfilament Proteins / metabolism
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Microscopy, Confocal
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Microscopy, Electron
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Microvilli / metabolism
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Microvilli / ultrastructure
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Phospholipase C beta / genetics
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Phospholipase C beta / metabolism
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Nicotinic / metabolism*
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Respiration*
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Reverse Transcriptase Polymerase Chain Reaction
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Taste
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Trachea / cytology
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Trachea / metabolism
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Trachea / physiology*
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Vesicular Acetylcholine Transport Proteins / metabolism
Substances
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Microfilament Proteins
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Receptors, G-Protein-Coupled
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Receptors, Nicotinic
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Slc18a3 protein, mouse
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Tas2R105 protein, mouse
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Tas2R108 protein, mouse
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Vesicular Acetylcholine Transport Proteins
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villin
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Green Fluorescent Proteins
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Choline O-Acetyltransferase
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Phospholipase C beta
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GNAT3 protein, mouse
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Heterotrimeric GTP-Binding Proteins