Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes
- aInstitute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
- bGerman Center for Lung Research, 35392 Giessen, Germany;
- cDepartment of Physiology, University of Otago, 9016 Dunedin, New Zealand;
- dInstitute of Animal Physiology, Justus-Liebig University, 35392 Giessen, Germany;
- eInstitute of Anatomy and Cell Biology, Philipps University, 35037 Marburg, Germany;
- fWalter-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilian University, 80336 Munich, Germany;
- gDepartment of Pharmacology, School of Pharmacy, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany; and
- hDepartment of Urology, Pediatric Urology, and Andrology, Justus-Liebig University, 35392 Giessen, Germany
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Edited by Scott J. Hultgren, Washington University School of Medicine, St. Louis, MO, and approved April 22, 2014 (received for review February 10, 2014)

Significance
We report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system. These cells exhibit structural markers of respiratory chemosensory cells (“brush cells”). They use the classical taste transduction cascade to detect potential hazardous compounds (bitter, umami, uropathogenic bacteria) and release acetylcholine in response. They lie next to sensory nerve fibers that carry acetylcholine receptors, and placing a bitter compound in the urethra enhances activity of the bladder detrusor muscle. Thus, monitoring of urethral content is linked to bladder control via a previously unrecognized cell type.
Abstract
Chemosensory cells in the mucosal surface of the respiratory tract (“brush cells”) use the canonical taste transduction cascade to detect potentially hazardous content and trigger local protective and aversive respiratory reflexes on stimulation. So far, the urogenital tract has been considered to lack this cell type. Here we report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system, but not in further centrally located parts of the urinary tract, such as the bladder, ureter, and renal pelvis. Urethral brush cells express bitter and umami taste receptors and downstream components of the taste transduction cascade; respond to stimulation with bitter (denatonium), umami (monosodium glutamate), and uropathogenic Escherichia coli; and release acetylcholine to communicate with other cells. They are approached by sensory nerve fibers expressing nicotinic acetylcholine receptors, and intraurethral application of denatonium reflexively increases activity of the bladder detrusor muscle in anesthetized rats. We propose a concept of urinary bladder control involving a previously unidentified cholinergic chemosensory cell monitoring the chemical composition of the urethral luminal microenvironment for potential hazardous content.
Footnotes
↵1K.D. and K.F. contributed equally to this work.
↵2T.B. and W.K. contributed equally to this work.
- ↵3To whom correspondence should be addressed. E-mail: wolfgang.kummer{at}anatomie.med.uni-giessen.de.
Author contributions: K.D., G.K.-C., T.B., and W.K. designed research; K.D., K.F., G.K.-C., M.F., M.A., A.R., T.P., L.R., I.J., L.W., M.W., J.K., T.B., and W.K. performed research; B.S., E.W., V.C., and T.G. contributed new reagents/analytic tools; K.D., K.F., G.K.-C., M.F., J.K., T.B., and W.K. analyzed data; and K.D., K.F., M.F., T.B., and W.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1402436111/-/DCSupplemental.