Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes.
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.
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Klaus
K
Deckmann
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Katharina
K
Filipski
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;German Center for Lung Research, 35392 Giessen, Germany;
Gabriela
G
Krasteva-Christ
Department of Physiology, University of Otago, 9016 Dunedin, New Zealand;Institute of Animal Physiology, Justus-Liebig University, 35392 Giessen, Germany;
Martin
M
Fronius
Institute of Animal Physiology, Justus-Liebig University, 35392 Giessen, Germany;
Mike
M
Althaus
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Amir
A
Rafiq
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Tamara
T
Papadakis
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Liane
L
Renno
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Innokentij
I
Jurastow
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Lars
L
Wessels
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;
Miriam
M
Wolff
Institute of Anatomy and Cell Biology, Philipps University, 35037 Marburg, Germany;
Burkhard
B
Schütz
German Center for Lung Research, 35392 Giessen, Germany;Institute of Anatomy and Cell Biology, Philipps University, 35037 Marburg, Germany;
Eberhard
E
Weihe
Walter-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilian University, 80336 Munich, Germany;
Vladimir
V
Chubanov
German Center for Lung Research, 35392 Giessen, Germany;Walter-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilian University, 80336 Munich, Germany;
Thomas
T
Gudermann
Department of Pharmacology, School of Pharmacy, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany; and.
Jochen
J
Klein
Department of Urology, Pediatric Urology, and Andrology, Justus-Liebig University, 35392 Giessen, Germany.
Thomas
T
Bschleipfer
Institute of Anatomy and Cell Biology, Justus-Liebig University, 35385 Giessen, Germany;German Center for Lung Research, 35392 Giessen, Germany; wolfgang.kummer@anatomie.med.uni-giessen.de.
Wolfgang
W
Kummer
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002628:Chemoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008871:Microvilli / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D018408:Patch-Clamp Techniques; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology; D011984:Sensory Receptor Cells / Q000166:cytology / Q000502:physiology; D013649:Taste / Q000502:physiology; D014059:Tongue / Q000166:cytology / Q000294:innervation / Q000502:physiology; D014521:Urethra / Q000166:cytology* / Q000294:innervation / Q000378:metabolism*; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology*; D014563:Urodynamics / Q000502:physiology; D019459:Urothelium / Q000166:cytology / Q000378:metabolism; D000098706:Taste Receptors, Type 2
D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D049452:Green Fluorescent Proteins; D000109:Acetylcholine