title: Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells.
abstract: Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting.
authors.affiliation: Department of Dermatology, University Medical Center, Freiburg 79104, Germany. ute.woelfle@uniklinik-freiburg.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Wölfle
authors.affiliation: Department of Pharmacology, Biocenter, Goethe-University, Frankfurt 60438, Germany. Floriana.Elsholz@gmx.de.
authors.forename: Floriana A
authors.initials: FA
authors.lastname: Elsholz
authors.affiliation: Dermatohistological Laboratory Dr.Laaff, Freiburg 79111, Germany. astrid.kersten@posteo.de.
authors.forename: Astrid
authors.initials: A
authors.lastname: Kersten
authors.affiliation: Department of Dermatology, University Medical Center, Freiburg 79104, Germany. birgit.haarhaus@uniklinik-freiburg.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Haarhaus
authors.affiliation: Department of Anatomy and Experimental Morphology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg 20246, Germany. uschumacher@uke.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.affiliation: Department of Dermatology, University Medical Center, Freiburg 79104, Germany. christoph.schempp@uniklinik-freiburg.de.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Schempp
mesh_terms: D020013:Calcium Signaling; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D010670:Phenylthiourea / Q000378:metabolism / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism*; D046888:Tissue Array Analysis; D014018:Tissue Distribution; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D010670:Phenylthiourea
keywords: bitter taste receptor; calcium influx; placental tissue