Cholinergic chemosensory cells in the trachea regulate breathing

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.airway sensory innervation | respiratory epithelium | jugular-nodose ganglion | bitter-tasting substances

Sense of Taste in the Gastrointestinal Tract

“…Krasteva et al reported that brush cells in the airway express bitter taste receptors and their downstream signaling molecules such as α-gustducin and PLCβ2 together with acetylcholine synthase (39). Furthermore, the study demonstrated that activation by a bitter substance releases acetylcholine, which eventually decreases the respiratory rate, indicating a biological function of a bitter substance through brush cells.…”

Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes

“…Respiratory chemosensory brush cells express elements of the canonical taste transduction cascade, including the taste-specific G protein α-gustducin, phospholipase C β2 (PLCβ2), and the transient potential receptor cation channel melanostatin 5 (TRPM5) (5,6,(15)(16)(17). These proteins are also expressed in urethras from ChAT-eGFP and WT mice (Fig.…”

“…Fluorescence microscopy and immunohistochemistry, pre-embedding immunohistochemistry, and EM, RT-PCR, and acetylcholine measurements were performed as described previously (6,48), with minor modifications. More details are provided in SI Materials and Methods.…”

“…In the respiratory tract, these brush cells serve as sentinels, using the canonical taste transduction cascade to monitor the mucosal lining fluid for potential harmful substances, such as "bitter" bacterial products, and evoking reflexes aimed at combating further ingression of such compounds, such as closure of ducts leading into adjacent compartments (vomeronasal organ) or respiratory reflexes (4)(5)(6)(7).…”

Lung Epithelial Healing: A Modified Seed and Soil Concept

“…The tracheobronchial epithelium is populated by multiple cell types including basal, ciliated, secretory (mucus or nonmucus), serous cells, brush cells (also termed cholinergic chemosensory cells [10] and solitary chemosensory cells [11]), and neuroendocrine cells. Among these cell types, basal, ciliated, and secretory cells account for the majority of cells within the epithelium and are the focus of our work and that of others.…”