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Author

Christian Kuhn

Bio: Christian Kuhn is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Medicine & TAS2R38. The author has an hindex of 14, co-authored 34 publications receiving 2973 citations.
Topics: Medicine, TAS2R38, Internal medicine, Taste, Receptor


Papers
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Journal ArticleDOI
TL;DR: The data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs, and some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness.
Abstract: Humans perceive thousands of compounds as bitter. In sharp contrast, only ;25 taste 2 receptors (TAS2R) bitter taste receptors have been identified, raising the question as to how the vast array of bitter compounds can be detected by such a limited number of sensors. To address this issue, we have challenged 25 human taste 2 receptors (hTAS2Rs) with 104 natural or synthetic bitter chemicals in a heterologous expression system. Thirteen cognate bitter compounds for 5 orphan receptors and 64 new compounds for previously identified receptors were discovered. Whereas some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness. Thus, 3 hTAS2Rs together were able to detect ;50% of the substances used. Conversely, though 63 bitter substances activated only 1–3 receptors, 19 compounds stimulated up to 15 hTAS2Rs. Our data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs.

870 citations

Journal ArticleDOI
TL;DR: Individual psychogenomic pathways for bitter taste are mapped by testing people with a variety of psychophysical tasks and linking their individual perceptions of the compounds PTC and propylthiouracil to the in vitro responses of their TAS2R38 receptor variants.

645 citations

Journal ArticleDOI
11 Mar 2010-Nature
TL;DR: These studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.
Abstract: Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion. Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a non-selective detector for a wide range of salts. Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system. Previously, we showed that four of the five basic taste qualities—sweet, sour, bitter and umami—are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses. Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCα in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.

549 citations

Journal ArticleDOI
TL;DR: In this paper, functional expression experiments in human embryonic kidney cells were conducted to show that saccharin and acesulfame K activate two members of the human TAS2R family at concentrations known to stimulate bitter taste.
Abstract: Weight-conscious subjects and diabetics use the sulfonyl amide sweeteners saccharin and acesulfame K to reduce their calorie and sugar intake. However, the intrinsic bitter aftertaste, which is caused by unknown mechanisms, limits the use of these sweeteners. Here, we show by functional expression experiments in human embryonic kidney cells that saccharin and acesulfame K activate two members of the human TAS2R family (hTAS2R43 and hTAS2R44) at concentrations known to stimulate bitter taste. These receptors are expressed in tongue taste papillae. Moreover, the sweet inhibitor lactisole did not block the responses of cells transfected with TAS2R43 and TAS2R44, whereas it did block the response of cells expressing the sweet taste receptor heteromer hTAS1R2-hTAS1R3. The two receptors were also activated by nanomolar concentrations of aristolochic acid, a purely bitter-tasting compound. Thus, hTAS2R43 and hTAS2R44 function as cognate bitter taste receptors and do not contribute to the sweet taste of saccharin and acesulfame K. Consistent with the in vitro data, cross-adaptation studies in human subjects also support the existence of common receptors for both sulfonyl amide sweeteners.

316 citations

Journal ArticleDOI
TL;DR: In this paper, the authors demonstrate the expression of the hTAS2R14 gene by RT-PCR analyses and in situ hybridisation in human circumvallate papillae.

202 citations


Cited by
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Journal ArticleDOI
TL;DR: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery.
Abstract: Background Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) an...

2,917 citations

Journal ArticleDOI
16 Nov 2006-Nature
TL;DR: The emerging picture of taste coding at the periphery is one of elegant simplicity, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes.
Abstract: The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.

1,330 citations

Journal ArticleDOI
TL;DR: This article aims to provide a comprehensive overview of the five main human GPCR families with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
Abstract: G protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and also the targets of many drugs. Understanding of the functional significance of the wide structural diversity of GPCRs has been aided considerably in recent years by the sequencing of the human genome and by structural studies, and has important implications for the future therapeutic potential of targeting this receptor family. This article aims to provide a comprehensive overview of the five main human GPCR families--Rhodopsin, Secretin, Adhesion, Glutamate and Frizzled/Taste2--with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.

1,247 citations

Journal ArticleDOI
TL;DR: The data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs, and some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness.
Abstract: Humans perceive thousands of compounds as bitter. In sharp contrast, only ;25 taste 2 receptors (TAS2R) bitter taste receptors have been identified, raising the question as to how the vast array of bitter compounds can be detected by such a limited number of sensors. To address this issue, we have challenged 25 human taste 2 receptors (hTAS2Rs) with 104 natural or synthetic bitter chemicals in a heterologous expression system. Thirteen cognate bitter compounds for 5 orphan receptors and 64 new compounds for previously identified receptors were discovered. Whereas some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness. Thus, 3 hTAS2Rs together were able to detect ;50% of the substances used. Conversely, though 63 bitter substances activated only 1–3 receptors, 19 compounds stimulated up to 15 hTAS2Rs. Our data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs.

870 citations

Journal ArticleDOI
16 Oct 2009-Cell
TL;DR: There is now persuasive evidence that tastant quality is mediated by labeled lines, whereby distinct and strictly segregated populations of taste receptor cells encode each of the taste qualities.

703 citations