Cholinergic chemosensory cells in the respiratory epithelium sense the luminal microenvironment

Recently, we have shown that brush cells of the trachea are cholinergic and affect respiration upon stimulation with cycloheximide, a bitter tasting substance. Here, using mice expressing eGFP under the control of the promoter of choline acetyltransferase (ChAT), we show the presence of identical solitary cholinergic villin-positive brush cells also in the mouse auditory tube. They also express the vesicular ACh transporter and proteins of the taste transduction pathway (α-gustducin and PLCβ2). Messenger RNA for bitter taste receptor (Tas2R) 105 and Tas2R108 involved in perception of the bitter substances cycloheximide and denatonium as well as in perception of acyl-homoserine lactones, bacterial quorum-sensing molecules, were detected in the respiratory epithelium. Using a transgenic mouse that expresses eGFP under the control of the promotor for the α3-subunit of the nicotinic ACh receptor, we identified direct contacts between α3+ neuronal fibres and brush cells in the auditory tube resembling those observed in the trachea. A subpopulation of these fibres is CGRP-immunoreactive. Functional analyses were performed in the trachea using a newly established model for investigation of respiration in spontaneously breathing anesthetized mice. DMPP, a nicotinic agonist, caused a drop in respiratory rate that was augmented by inhibition of nicotinic receptors with mecamylamine. Acyl-homoserine lactone elicited an epithelium-dependent drop in respiratory rate which was abolished by pretreatment with mecamylamine.

We conclude that respiratory epithelial brush cells are chemosensory cholinergic cells that sense the composition of the luminal microenvironment and communicate this to the CNS via ACh release and nicotinic stimulation of sensory neurons.