Three TAS2R Bitter Taste Receptors Mediate the Psychophysical Responses to Bitter Compounds of Hops (Humulus lupulus L.) and Beer

Intelmann, Daniel; Batram, Claudia; Kühn, Christina; Haseleu, Gesa; Meyerhof, Wolfgang; Hofmann, Thomas

doi:10.1007/s12078-009-9049-1

Cited by 89 publications

(119 citation statements)

References 44 publications

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“…We often observed that compounds expected to activate a hTAS2R under study actually failed to do so (Bufe et al, 2002(Bufe et al, , 2005Brockhoff et al, 2007;Intelmann et al, 2009). These compounds include glucopyranosides as activators of hTAS2R16, thioamides, carbamides, or isothiocyanates as activators of hTAS2R38, and sesquiterpene lactones as activators of hTAS2R46.…”

Section: Discussionmentioning

confidence: 99%

“…Agonists recently identified (Dotson et al, 2008;Intelmann et al, 2009;Slack et al, 2010) were applied at EC 90 concentration. Because of low potency, agonists for hTAS2R5, hTAS2R7, and hTAS2R13 were used at their maximum applicable concentration that did not cause unspecific fluorescence signals in control cells.…”

Section: Discussionmentioning

confidence: 99%

“…Andrographolide, aristolochic acids, brucine, chloramphenicol, chloroquine diphosphate salt, colchicine, cromolyn, denatonium benzoate, denatonium saccharide, epigallocatechin gallate, ofloxacin, phenylthiocarbamide, picrotoxinin, quinine sulfate, D-salicin, and strychnine have been purchased in the highest purity from SigmaAldrich. Absinthin, 3␤-hydroxypelenolide (3HP) from mountain wormwood (Artemisia absinthium L.), trans-isocohumulone, and cohumulone have been available from previous studies (Brockhoff et al, 2007;Intelmann et al, 2009). Costunolide has been purchased from LGC Standarts.…”

Section: Methodsmentioning

confidence: 99%

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Receptor Agonism and Antagonism of Dietary Bitter Compounds

Brockhoff¹,

Behrens²,

Roudnitzky³

et al. 2011

J. Neurosci.

100

104

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Food contains complex blends of structurally diverse bitter compounds that trigger bitterness through activation of one or more of the ϳ25 human TAS2 bitter taste receptors. It remains unsolved, however, whether the perceived bitterness of binary bitter-compound mixtures can be considered an additive function of all bitter-inducing chemicals in the mouth, suggesting that little mutual interaction takes place among bitter substances or if mixture suppression and synergism occurs. Here we report on two natural sesquiterpene lactones from edible plants, which stimulate distinct sets of hTAS2Rs in transfected cells. Both chemicals also robustly inhibit different but overlapping subsets of agonist-activated hTAS2Rs. These findings demonstrate that mixtures of bitter compounds, because they normally occur in human foodstuff, likely elicit bitter perception in a complex and not in a merely additive manner. An unexpected implication of this discovery is that, during evolution, the naturally occurring bitter taste receptor antagonists have shaped some of the pharmacological properties of the receptors, such as overlapping recognition profiles and breadth of tuning.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Receptor Agonism and Antagonism of Dietary Bitter Compounds

Brockhoff¹,

Behrens²,

Roudnitzky³

et al. 2011

J. Neurosci.

100

104

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“…Noncommercial bitter terpenoids were obtained by isolation from their plant sources (107)(108)(109)(110)(111)(112). All other substances were available from previous studies (32,37). For detailed information about manufacturers and applied concentrations, see supplemental Table 1S.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

Lossow

Hübner

Roudnitzky

et al. 2016

Journal of Biological Chemistry

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174

257

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One key to animal survival is the detection and avoidance of potentially harmful compounds by their bitter taste. Variable numbers of taste 2 receptor genes expressed in the gustatory end organs enable bony vertebrates (Euteleostomi) to recognize numerous bitter chemicals. It is believed that the receptive ranges of bitter taste receptor repertoires match the profiles of bitter chemicals that the species encounter in their diets. Human and mouse genomes contain pairs of orthologous bitter receptor genes that have been conserved throughout evolution. Moreover, expansions in both lineages generated species-specific sets of bitter taste receptor genes. It is assumed that the orthologous bitter taste receptor genes mediate the recognition of bitter toxins relevant for both species, whereas the lineagespecific receptors enable the detection of substances differently encountered by mice and humans. By challenging 34 mouse bitter taste receptors with 128 prototypical bitter substances in a heterologous expression system, we identified cognate compounds for 21 receptors, 19 of which were previously orphan receptors. We have demonstrated that mouse taste 2 receptors, like their human counterparts, vary greatly in their breadth of tuning, ranging from very broadly to extremely narrowly tuned receptors. However, when compared with humans, mice possess fewer broadly tuned receptors and an elevated number of narrowly tuned receptors, supporting the idea that a large receptor repertoire is the basis for the evolution of specialized receptors. Moreover, we have demonstrated that sequence-orthologous bitter taste receptors have distinct agonist profiles. Species-specific gene expansions have enabled further diversification of bitter substance recognition spectra.The plethora of natural compounds that taste bitter for humans comprises numerous chemicals with pharmacological activities that can make them powerful toxins, such as the alkaloids strychnine and colchicine or the sesquiterpene lactone picrotoxinin (1). However, compounds believed to exert health-beneficial effects such as the antioxidative phytoestrogen genistein from soy (2), the analgesic drug acetaminophen (3), or various polyphenols also taste bitter (4). To avoid ingestion of bitter substances that would pose a threat to organisms, efficient recognition and rejection mechanisms have developed throughout the animal kingdom. In bony vertebrates (Euteleostomi), the avoidance of bitter compounds is centered on taste receptors that detect potentially harmful substances with high accuracy and adequate sensitivity (5). Vertebrate bitter taste receptors, called taste 2 receptors (TAS2R (human) or Tas2r (murine)), 2 are G protein-coupled receptors only remotely related to other classes of this large and enormously versatile receptor family (6 -10). During evolution the first Tas2r genes appeared in the genomes of bony fish (11). In higher vertebrates frequent independent expansions and pseudogenization events resulted in differently sized Tas2r gene repertoires (12). Cons...

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“…Human bitter taste threshold concentrations of degradation products 3 a-8 a: The iso-aacids (2, 3; Scheme 1) are commonly known to exhibit intense bitterness [48] and to be the primary contributors to the attractive bitter taste of fresh beer. [2] To gain first insight into the impact on taste of the storageinduced trans-iso-a-acid transformation products identified above, bitter taste recognition threshold concentrations were determined for 4 a-8 a as well as for their precursor 3 a by .…”

Section: Wwwchemeurjorgmentioning

confidence: 99%

Structures of Storage‐Induced Transformation Products of the Beer’s Bitter Principles, Revealed by Sophisticated NMR Spectroscopic and LC–MS Techniques

Intelmann

Kummerlöwe

Haseleu

et al. 2009

Chemistry A European J

Self Cite

107

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Besides undesirable changes in the attractive aroma, a significant decrease in the intensity of the bitterness as well as a change of the taste into a lingering, harsh bitterness has long been known as a shelf-life limiting factor of beer. Multiple studies have demonstrated that the aging of beer induces a decrease of the total amount of cis- and trans-iso-alpha-acids, the well-known bitter principles of beer. Although the trans-iso-alpha-acids exclusively, not the cis-iso-alpha-acids, were found to be degraded upon storage of beer, the key transformation products formed exclusively from the trans isomers in beer are not known. In the present study, suitable model experiments followed by LC-MS/MS and sophisticated NMR spectroscopic experiments, including the measurement of residual dipolar couplings (RDCs) in gel-based alignment media as well as a novel broadband and B(1)-field-compensated incredible natural abundance double-quantum transfer experiment (INADEQUATE) pulse sequence, enabled the identification of a series of previously unknown trans-specific iso-alpha-acid transformation products, namely, tricyclocohumol, tricyclocohumene, isotricyclocohumene, tetracyclocohumol, and epitetracyclocohumol, respectively. HPLC-MS/MS analysis of these compounds, which exhibit the aforementioned harsh lingering bitter taste and have threshold concentrations ranging from 5 to 70 micromol L(-1), confirmed their generation during aging of beer and, for the first time, explained the storage-induced changes of the beer's bitter taste on a molecular level.

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Three TAS2R Bitter Taste Receptors Mediate the Psychophysical Responses to Bitter Compounds of Hops (Humulus lupulus L.) and Beer

Cited by 89 publications

References 44 publications

Receptor Agonism and Antagonism of Dietary Bitter Compounds

Receptor Agonism and Antagonism of Dietary Bitter Compounds

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

Structures of Storage‐Induced Transformation Products of the Beer’s Bitter Principles, Revealed by Sophisticated NMR Spectroscopic and LC–MS Techniques

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