Chemosensory epithelial cells in the urethra: sentinels of the urinary tract

A peculiar cell type of the respiratory and gastrointestinal epithelia, originally termed "brush cell" or "tuft cell" by electron microscopists because of its apical tuft of microvilli, utilizes the canonical bitter taste transduction cascade known from oropharyngeal taste buds to detect potential hazardous compounds, e.g. bacterial products. Upon stimulation, this cell initiates protective reflexes and local inflammatory responses through release of acetylcholine and chemokines. Guided by the understanding of these cells as sentinels, they have been newly discovered at previously unrecognized anatomical locations, including the urethra. Solitary cholinergic urethral cells express canonical taste receptors and are polymodal chemosensors for certain bitter substances, glutamate (umami) and uropathogenic Escherichia coli. Intraurethral bitter stimulation triggers cholinergic reflex activation of bladder detrusor activity, which is interpreted as cleaning flushing of the urethra. The currently known scenario suggests the presence of at least two more urethral chemosensory cell types: non-cholinergic brush cells and neuroendocrine serotonergic cells. The potential implications are enormous and far reaching, as these cells might be involved in monitoring and preventing ascending urinary tract infection and triggering of inappropriate detrusor activity. However, although appealing, this is still highly speculative, since the actual number of distinct chemosensory cell types needs to be finally clarified, as well as their embryological origin, developmental dynamics, receptor equipment, modes of signalling to adjacent nerve fibres and other cells, repertoire of chemo- and cytokines, involvement in pathogenesis of diseases and many other aspects.