title: Cholinergic urethral brush cells are widespread throughout placental mammals.
abstract: We previously identified a population of cholinergic epithelial cells in murine, human and rat urethrae that exhibits a structural marker of brush cells (villin) and expresses components of the canonical taste transduction signaling cascade (α-gustducin, phospholipase Cβ2 (PLCβ2), transient receptor potential cation channel melanostatin 5 (TRPM5)). These cells serve as sentinels, monitoring the chemical composition of the luminal content for potentially hazardous compounds such as bacteria, and initiate protective reflexes counteracting further ingression. In order to elucidate cross-species conservation of the urethral chemosensory pathway we investigated the occurrence and molecular make-up of urethral brush cells in placental mammals. We screened 11 additional species, at least one in each of the five mammalian taxonomic units primates, carnivora, perissodactyla, artiodactyla and rodentia, for immunohistochemical labeling of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), villin, and taste cascade components (α-gustducin, PLCβ2, TRPM5). Corresponding to findings in previously investigated species, urethral epithelial cells with brush cell shape were immunolabeled in all 11 mammals. In 8 species, immunoreactivities against all marker proteins and ChAT were observed, and double-labeling immunofluorescence confirmed the cholinergic nature of villin-positive and chemosensory (TRPM5-positive) cells. In cat and horse, these cells were not labeled by the ChAT antiserum used in this study, and unspecific reactions of the secondary antiserum precluded conclusions about ChAT-expression in the bovine epithelium. These data indicate that urethral brush cells are widespread throughout the mammalian kingdom and evolved not later than about 64.5millionyears ago.
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany. Electronic address: Klaus-Deckmann@gmx.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Deckmann
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany; German Center for Lung Research (DZL), Germany; Institute for Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, Koellikerstrasse 6, 97070 Wuerzburg, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Krasteva-Christ
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Rafiq
authors.affiliation: Institute of Veterinary Pathology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Herden
authors.affiliation: German Center for Lung Research (DZL), Germany; Pathology Unit, German Primate Center, Leibniz-Institute for Primate Research, 37077 Goettingen, Germany; Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), 30625 Hannover , Germany.
authors.forename: Judy
authors.initials: J
authors.lastname: Wichmann
authors.affiliation: German Center for Lung Research (DZL), Germany; Pathology Unit, German Primate Center, Leibniz-Institute for Primate Research, 37077 Goettingen, Germany; Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), 30625 Hannover , Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Knauf
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany; German Center for Lung Research (DZL), Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Nassenstein
authors.affiliation: BFS, Institute for Parasitology, Justus-Liebig-University, 35392 Giessen, Germany.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Grevelding
authors.affiliation: Institute for General Zoology and Developmental Biology, Justus-Liebig-University, 35385 Giessen, Germany.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Dorresteijn
authors.affiliation: Walter-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Chubanov
authors.affiliation: German Center for Lung Research (DZL), Germany; Walter-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Klinikum Weiden, 92637 Weiden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bschleipfer
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany; German Center for Lung Research (DZL), Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008322:Mammals / Q000502:physiology*; D010802:Phylogeny; D013045:Species Specificity; D014521:Urethra / Q000166:cytology*
chemical_list: D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine
keywords: Acetylcholine; Chemosensory; Placental mammals; Urethra