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Bitter taste receptors

Louisa Stern, Nathalia Giese, Thilo Hackert, Oliver Strobel, Peter Schirmacher, Klaus Felix, Matthias M Gaida
Bitter taste receptors (T2Rs) are G-protein coupled transmembrane proteins initially identified in the gustatory system as sensors for the taste of bitter. Recent evidence on expression of these receptors outside gustatory tissues suggested alternative functions, and there is growing interest of their potential role in cancer biology. In this study, we report for the first time, expression and functionality of the bitter receptor family member T2R10 in both human pancreatic ductal adenocarcinoma (PDAC) tissue and PDAC derived cell lines...
2018: Journal of Cancer
Ava Yuan Xue, Antonella Di Pizio, Anat Levit, Tali Yarnitzky, Osnat Penn, Tal Pupko, Masha Y Niv
The 25 human bitter taste receptors (hT2Rs) recognize thousands of structurally and chemically diverse bitter substances. The binding modes of human bitter taste receptors hT2R10 and hT2R46, which are responsible for strychnine recognition, were previously established using site-directed mutagenesis, functional assays, and molecular modeling. Here we construct a phylogenetic tree and reconstruct ancestral sequences of the T2R10 and T2R46 clades. We next analyze the binding sites in view of experimental data to predict their ability to recognize strychnine...
2018: Frontiers in Molecular Biosciences
Jie Qian, Shobha Mummalaneni, James Larsen, John R Grider, Andrew I Spielman, Mehmet Hakan Özdener, Vijay Lyall
In rodents, CHRNs are involved in bitter taste transduction of nicotine and ethanol. Currently, it is not clear if CHRNs are expressed in human taste cells and if they play a role in transducing the bitter taste of nicotine and ethanol or in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of CHRNs in HBO cells. Using molecular techniques, we demonstrate that a subset of HBO cells express CHRNs that also co-express TRPM5, T1R3 or T2R38. Exposing HBO cells to nicotine or ethanol acutely or to nicotine chronically induced a differential increase in the expression of CHRN mRNA and protein in a dose- and time-dependent manner...
2018: PloS One
Ali Asgar Bohra, Benjamin R Kallman, Heinrich Reichert, K VijayRaghavan
Drosophila has become an excellent model system for investigating the organization and function of the gustatory system due to the relatively simple neuroanatomical organization of its brain and the availability of powerful genetic and transgenic technology. Thus, at the molecular and cellular levels, a great deal of insight into the peripheral detection and coding of gustatory information has already been attained. In contrast, much less is known about the central neural circuits that process this information and induce behaviorally appropriate motor output...
February 21, 2018: Current Biology: CB
Federica Pollastro, Maria Talmon, Simone Gaeta, Silvia Rossi, Annalisa Lopatriello, Luigia Grazia Fresu
The discovery of taste receptors hTAS2Rs expression in extra oral tissue, especially in the gastrointestinal tract and in the respiratory system, has endowed bitter receptors of functionalities that exceed the simple perception of taste and flavour. In particular, stimulation of hTAS2Rs by bitter agents in the airway smooth muscle triggers bronchodilation of possible pharmacological relevance. To study the receptor localization in pulmonary smooth muscle cells and to investigate their biological response to hTAS2R38 activation, we have developed a fluorescent probe for hTAS2R38 starting from the sesquiterpene lactone costunolide, available in multigram amounts from Artemisia umbelliformis Lam...
February 27, 2018: Fitoterapia
Giorgia Sollai, Maurizio Biolchini, Roberto Crnjar
In the peripheral taste system of insects, the responsiveness of gustatory receptor neurons (GRNs) depends on several factors, such as larval instar, feeding history, physiological state and time of day. To study the role of the feeding history, the spike activity of the maxillary taste chemosensilla in the larvae of two related species of Lepidoptera (Papilio machaon L. and Papilio hospiton Géné) raised on different host plants, was recorded with electrophysiological techniques after stimulation with simple stimuli (sugars, bitters and inorganic salt) and host plant saps, with the aim of cross-comparing their response patterns and evaluating any effects of different feeding histories...
February 15, 2018: Journal of Insect Physiology
Antonella Di Pizio, Nitzan Shy, Maik Behrens, Wolfgang Meyerhof, Masha Y Niv
Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors ( Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste...
2018: Frontiers in Molecular Biosciences
Ping Feng, Rui-Jian Luo
Among the five basic tastes (umami, sweet, bitter, salty and sour), the perception of bitterness is believed to protect animals from digesting toxic and harmful substances, thus it is vital for animal survival. The taste of bitterness is triggered by the interaction between bitter substances and bitter taste receptors, which are encoded by Tas2rs. The gene numbers vary largely across species to meet different demands. So far, several ligands of bitter receptors have been identified in primates. They also discovered that the selective pressure of certain bitter taste receptor genes vary across taxa, genes or even different functional regions of the gene...
February 20, 2018: Yi Chuan, Hereditas
Yumei Qin, Sunil K Sukumaran, Masafumi Jyotaki, Kevin Redding, Peihua Jiang, Robert F Margolskee
Mouse taste receptor cells survive from 3-24 days, necessitating their regeneration throughout adulthood. In anterior tongue, sonic hedgehog (SHH), released by a subpopulation of basal taste cells, regulates transcription factors Gli2 and Gli3 in stem cells to control taste cell regeneration. Using single-cell RNA-Seq we found that Gli3 is highly expressed in Tas1r3-expressing taste receptor cells and Lgr5+ taste stem cells in posterior tongue. By PCR and immunohistochemistry we found that Gli3 was expressed in taste buds in all taste fields...
February 7, 2018: PLoS Genetics
Sean D Schoville, Yolanda H Chen, Martin N Andersson, Joshua B Benoit, Anita Bhandari, Julia H Bowsher, Kristian Brevik, Kaat Cappelle, Mei-Ju M Chen, Anna K Childers, Christopher Childers, Olivier Christiaens, Justin Clements, Elise M Didion, Elena N Elpidina, Patamarerk Engsontia, Markus Friedrich, Inmaculada García-Robles, Richard A Gibbs, Chandan Goswami, Alessandro Grapputo, Kristina Gruden, Marcin Grynberg, Bernard Henrissat, Emily C Jennings, Jeffery W Jones, Megha Kalsi, Sher A Khan, Abhishek Kumar, Fei Li, Vincent Lombard, Xingzhou Ma, Alexander Martynov, Nicholas J Miller, Robert F Mitchell, Monica Munoz-Torres, Anna Muszewska, Brenda Oppert, Subba Reddy Palli, Kristen A Panfilio, Yannick Pauchet, Lindsey C Perkin, Marko Petek, Monica F Poelchau, Éric Record, Joseph P Rinehart, Hugh M Robertson, Andrew J Rosendale, Victor M Ruiz-Arroyo, Guy Smagghe, Zsofia Szendrei, Gregg W C Thomas, Alex S Torson, Iris M Vargas Jentzsch, Matthew T Weirauch, Ashley D Yates, George D Yocum, June-Sun Yoon, Stephen Richards
The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation...
January 31, 2018: Scientific Reports
Elie Chamoun, Joy M Hutchinson, Owen Krystia, Julia A Mirotta, David M Mutch, Andrea C Buchholz, Alison M Duncan, Gerarda Darlington, Jess Haines, David W L Ma
Snacking is an integral component of eating habits in young children that is often overlooked in nutrition research. While snacking is a substantial source of calories in preschoolers' diets, there is limited knowledge about the factors that drive snacking patterns. The genetics of taste may help to better understand the snacking patterns of children. The rs1761667 single nucleotide polymorphism (SNP) in the CD36 gene has been linked to fat taste sensitivity, the rs35874116 SNP in the TAS1R2 gene has been related to sweet taste preference, and the rs713598 SNP in the TAS2R38 gene has been associated with aversion to bitter, green leafy vegetables...
January 30, 2018: Nutrients
Axel Wolf, Bertold Renner, Peter V Tomazic, Christian A Mueller
OBJECTIVES: Recent research has shown that taste receptors in airway epithelial cells are involved in defending against upper respiratory tract infection. The aim of the present study was to investigate gustatory function in patients with chronic rhinosinusitis (CRS). METHODS: Taste function was assessed using the extended "taste strip" test in 37 patients with CRS (20 males, 17 females; mean age = 32.1 years; range, 20-82 years) and 135 healthy controls (70 males, 65 females; mean age = 29...
January 1, 2018: Annals of Otology, Rhinology, and Laryngology
Andrew I Spielman, Joseph G Brand
Taste receptor cells in the tongue are epithelial in nature and turnover frequently. Taste receptor cell-associated neurons carrying bitter, sweet or sour signals never turnover and are hardwired to specific gustatory centers in the brain. How can ever-changing bitter or sweet receptors find never-changing neurons that must match the specificity of the signal? This article reviews a recent paper published in Nature (Lee et al., 2017, 548:330-333) that identified two molecules belonging to the semaphorin axon guidance family of molecules (SEMA3A and SEMA7A) that help maintain the "labelled line principle" between peripheral bitter or sweet receptors and their respective central projection area in the gustatory center...
January 24, 2018: Oral Diseases
Xiao Yue, Jie Liang, Fu Gu, Dongshu Du, Fuxue Chen
Glucagon-like peptide-1 (GLP-1) is involved in the regulation of insulin secretion and glucose homeostasis. GLP-1 release is stimulated when berberine interacts with a novel G protein family (TAS2Rs) in enteroendocrine cells. In this study, we used STC-1 cells and examined a marked increase in Ca2+ in response to various bitter compounds. Ca2+ responses to traditional Chinese medicine extracts, including berberine, phellodendrine and coptisine, in STC-1 cells were suppressed by the phospholipase C (PLC) inhibitor U-73122, suggesting the involvement of bitter taste receptors in changing the physiological status of enteroendocrine cells in a PLC-dependent manner...
January 23, 2018: Molecular and Cellular Biochemistry
Kun Liu, Appalaraju Jaggupilli, Dhanaraj Premnath, Prashen Chelikani
Bitter taste receptors (T2Rs) are a group of 25 G protein-coupled receptors (GPCRs) in humans. The cognate agonists and the mechanism of ligand binding to the majority of the T2Rs remain unknown. Here we report the first structure-function analysis of T2R7 and study the ability of this receptor to bind to different agonists by site-directed mutagenesis. Screening of ligands for T2R7 in calcium based assays lead to the identification of novel compounds that activate this receptor. Quinine, diphenidol, dextromethorphan and diphenhydramine showed substantial activation of T2R7...
January 18, 2018: Biochimica et Biophysica Acta
Fabian Moine, Julien Brechbühl, Monique Nenniger Tosato, Manon Beaumann, Marie-Christine Broillet
BACKGROUND: The mouse Grueneberg ganglion (GG) is an olfactory subsystem specialized in the detection of volatile heterocyclic compounds signalling danger. The signalling pathways transducing the danger signals are only beginning to be characterized. RESULTS: Screening chemical libraries for compounds structurally resembling the already-identified GG ligands, we found a new category of chemicals previously identified as bitter tastants that initiated fear-related behaviours in mice depending on their volatility and evoked neuronal responses in mouse GG neurons...
January 18, 2018: BMC Biology
L Vancleef, T Thijs, F Baert, L J Ceulemans, E Canovai, Q Wang, S Steensels, A Segers, R Farré, J Pirenne, M Lannoo, J Tack, I Depoortere
SCOPE: The satiation properties of proteins involve effects on gut peptide release and gastrointestinal motility which may be altered during obesity. This study compared the in vitro response and role of amino acid (AA) taste receptors (TASR) in the effect of AAs and a casein hydrolysate on ghrelin release and smooth muscle (SM) contractions in the proximal gut of lean and obese patients. METHODS AND RESULTS: Basal ghrelin release, measured from mucosal segments, was maximal in the fundus and decreased distally...
January 11, 2018: Molecular Nutrition & Food Research
Xu Zhang, Liansheng Qiao, Yankun Chen, Bowen Zhao, Yu Gu, Xiaoqian Huo, Yanling Zhang, Gongyu Li
The metabotropic glutamate receptors (mGluRs) are known as both synaptic receptors and taste receptors. This feature is highly similar to the Property and Flavor theory of Traditional Chinese medicine (TCM), which has the pharmacological effect and flavor. In this study, six ligand based pharmacophore (LBP) models, seven homology modeling models, and fourteen molecular docking models of mGluRs were built based on orthosteric and allosteric sites to screening potential compounds from Traditional Chinese Medicine Database (TCMD)...
January 10, 2018: International Journal of Molecular Sciences
Tamami Haraguchi, Takahiro Uchida, Miyako Yoshida, Honami Kojima, Masaaki Habara, Hidekazu Ikezaki
The purpose of this study was to examine the ability of the artificial taste sensor to evaluate the bitterness of drugs by comparing the responses of the taste sensor with documented responses of human TASTE2 receptors (hTAS2Rs). For this purpose 22 bitter compounds, used as ingredients of pharmaceutical medicines in Japan and known ligands of hTAS2Rs, were selected for testing. Their solutions (0.01, 0.03, 0.1 mM) were evaluated by five different taste sensors (AC0, AN0, BT0, C00, AE1). Correlations between physicochemical parameters of the compounds and the responses of the taste sensors and hTAS2Rs were evaluated...
2018: Chemical & Pharmaceutical Bulletin
Debarghya Dutta Banik, Laura E Martin, Marc Freichel, Ann-Marie Torregrossa, Kathryn F Medler
Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. Transient receptor potential melastatin 5 (TRPM5), a sodium-selective TRP channel, functions as a common downstream component in sweet, bitter, and umami signaling pathways. In the absence of TRPM5, mice have a reduced, but not abolished, ability to detect stimuli, suggesting that a TRPM5-independent pathway also contributes to these signals. Here, we identify a critical role for the sodium-selective TRP channel TRPM4 in taste transduction...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
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