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.
Highlights
Sweet and bitter taste receptors (TAS2Rs) can be summarized as highly conserved G protein-coupled receptors (GPCRs)
Very recently it could be demonstrated that persons with the TAS2R38 taster variant get less bacterial infections, because the bacterial components acyl-homoserine lactones (AHLs) activate these bitter taste receptors in upper respiratory epithelial cells [13,14]
TAS2Rs were expressed in mucous epithelial cells of the tongue and outside the gustatory system in epithelial cells of the colon and stomach, upper respiratory tract, in Purkinje cells of the cerebellum and in the cornified squamous epithelium of the skin [13,14,15,17,19]
Summary
Sweet and bitter taste receptors (TAS2Rs) can be summarized as highly conserved G protein-coupled receptors (GPCRs). These receptors are present in insects (Drosophila) as well as in vertebrates ranging from fish to man [1,2,3,4], they possess structural differences. This study showed that local diet had no effect on the evolution of any of the PTC-sensitivity gene variants This proves that TAS2R38 must have other important roles in physiological processes than just warning for toxins, otherwise these variants wouldn’t exist anymore [12]. Very recently it could be demonstrated that persons with the TAS2R38 taster variant get less bacterial infections, because the bacterial components acyl-homoserine lactones (AHLs) activate these bitter taste receptors in upper respiratory epithelial cells [13,14]. (MRP1) transporter that is clinically used to treat gout in humans or is co-administered with antibiotics and chemotherapeutics to reduce their excretion
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