TAS2R14
receptor / receptor-tas2r14
TAS2R14 is a human bitter taste receptor subtype with a notably broad agonist spectrum. Quinine agonism (threshold 10 µM) is curated by the IUPHAR/BPS Guide to PHARMACOLOGY from Meyerhof 2010.
On this page (6 sections)
Reading the bitterness
TAS2R14 is one of the human bitter taste receptor subtypes with a notably broad agonist spectrum. In heterologous-expression screening assays, quinine has been recorded to activate human TAS2R14 at a threshold of 10 micromolar. This value is curated by the IUPHAR/BPS Guide to PHARMACOLOGY database, and it is important to note that this represents database-level interpretation of a single primary study.
Response to tea catechins has also been confirmed in assays using cultured cells expressing hTAS2R14. The authors of this study stated 「以前はhTAS2R39の活性化のみが報告されていた」 (in translation: "previously, only hTAS2R39 activation had been reported"), positioning catechins as a novel finding that activates not only hTAS2R39 but also hTAS2R14. Response by compound was as follows: catechin showed activity at a threshold of 500 micromolar; epicatechin (EC) showed weak and uncertain activity at the same threshold of 500 micromolar; epicatechin gallate (ECG) showed clear activity at a threshold of 125 micromolar; epigallocatechin (EGC) showed no activity; and epigallocatechin gallate (EGCG) showed activity at a threshold of 250 micromolar. Half-maximal effective concentration (EC50) could not be calculated for any of them.
TAS2R14 is broadly involved with bitter-tasting clinical drugs. Following pharmacophore and shape-based virtual screening, calcium imaging in TAS2R14-transfected HEK293 cells has been reported to confirm that 15 clinical drugs based on computational prediction activate TAS2R14, with an in vitro prediction success rate of 30 to 80 percent. This report also states that the hERG potassium channel emerged as a common off-target among these bitter drugs. This information is at the abstract stage, and individual drug names, test concentrations, and efficacy values cannot be confirmed from this material.
In a cell-based assay using 「正山小種」(Lapsang Souchong) tea extract before the pine-smoke withering process as the index of TAS2R14 activation, guaiacol and alpha-terpineol have been reported to each show antagonistic activity. Guaiacol reduced intracellular calcium signal by 37 percent and alpha-terpineol by 21 percent, and quantum chemical calculations suggest non-covalent interactions through hydrogen bonding and van der Waals forces. This is information at the abstract stage of a single study, and the full text has not been confirmed.
Sources for this overview
IUPHAR/BPS Guide to PHARMACOLOGY: quinine (ligand 2510) interaction records
Checked for this overview: Used to support the basis for the activation record of quinine at a threshold of 10 micromolar.
Checked for this overview: Used to support the basis for compound-specific catechin response and threshold values.
The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14
Checked for this overview: Used to support the basis for the statement that 15 clinical drugs showed a prediction success rate of 30 to 80 percent.
Role of smoke withering process in the bitterness amelioration effect on smoked Lapsang Souchong tea
Checked for this overview: Used to support the basis for the antagonistic rate statement of 37 percent reduction by guaiacol. / Used to support the basis for the antagonistic rate statement of 21 percent reduction by terpineol.
Follow the connections
quinine →activates→ TAS2R14
tea catechins →activates→ TAS2R14
guaiacol →antagonizes→ TAS2R14
Structured claims — open a section to read each claim's confidence, evidence and limits
Mechanism and receptors (6)
Scope: A heterologous-expression screen curated by IUPHAR/BPS GtoPdb (25 hTAS2R x 104 compounds)
Note: Read at the level of a curated database only, from a single primary study. Meyerhof 2010's full text/supplement (paywalled) is reported to characterize a broader set of quinine receptors, but this is not claimed here.
Show data
compound-quinine —activates→ receptor-tas2r14Scope: A virtual screening of clinical drugs against the broadly tuned TAS2R14, verified in transfected HEK293 cells
Note: Abstract only. The identities of the 15 drugs, the concentrations tested, and potency values have not been obtained. The paper is not indexed in PMC. The abstract further states that the hERG potassium channel emerged as an off-target common to these bitter drugs.
Show data
receptor-tas2r14 —is_activated_in_vitro_by→ "15 clinical drugs identified by pharmacophore- and shape-based virtual screening followed by calcium imaging in TAS2R14-transfected HEK293 cells (an in vitro success rate of 30-80% for the computational predictions)"Scope: A heterologous-expression cell receptor assay (cultured cells expressing hTAS2R14)
Show data
compound-catechins —activate→ receptor-tas2r14Scope: A cell-based assay using 「正山小種」(Lapsang Souchong) tea extract before the pine-smoke withering process as the index of TAS2R14 activation.
Note: Guaiacol has been reported to antagonistically inhibit TAS2R14 activation induced by tea extract from Lapsang Souchong before the pine-smoking withering process in the form of reducing intracellular calcium signal by 37 percent. Quantum chemical calculations suggest non-covalent interactions through hydrogen bonding and van der Waals forces. This is information from a single study at the abstract stage, and the full text has not been confirmed.
Show data
compound-guaiacol —antagonizes→ receptor-tas2r14Scope: As above.
Note: Alpha-terpineol has been reported to reduce the calcium signal from TAS2R14 activation in the same assay by 21 percent. This is information from a single study at the abstract stage, and the full text has not been confirmed.
Show data
compound-alpha-terpineol —antagonizes→ receptor-tas2r14Scope: Layer: cell. Effects on TAS2R14 were measured with a cell-based calcium-imaging assay.
Note: Full text not checked; confirmed from the full abstract as posted on Semantic Scholar. Separately from the 2 existing claims (confirmation of reduced bitterness, and the decrease in bitter phenolics), this adds a mechanism by which the aroma compounds themselves directly suppress the bitterness signal at the receptor level.
Show data
process-pine-smoke-withering —reduces→ receptor-tas2r14