TAS2R46
receptor / receptor-tas2r46
TAS2R46 is a subtype of the human bitter taste receptors.
On this page (7 sections)
Reading the bitterness
TAS2R46 is one of the subtypes of bitter taste receptors that humans possess. This receptor is characterized as a 「広域に調律された」 (in translation: "broadly tuned") receptor that responds to a wide range of bitter compounds with different chemical structures. It responds not only to sesquiterpene lactones but also to clerodane and labdane diterpenes, and further to strychnine and denatonium, which serve as reference bitter compounds. The compound that first identified this receptor from the orphan state was also a sesquiterpene lactone, harboside D.
In a study comparing sesquiterpene lactones derived from chicory, lactucopyrin activated this receptor at the lowest concentration. With a threshold of 0.03 µM and EC50 of 0.35±0.06 µM, it was the most sensitive among the receptor-compound combinations reported in the same study. The related lactucin required higher concentrations, with a threshold of 1 µM and EC50 of 8.85±1.17 µM. However, since TAS2R46 is a receptor that responds broadly to sesquiterpene lactones in general, this high sensitivity is not evidence of selectivity specific to lactucopyrin alone.
Absinthin, the bitter compound of wormwood (Artemisia absinthium), is also registered in pharmacology databases as one of the compounds that activates TAS2R46. Its affinity is documented as a value equivalent to approximately 10 µM, based on prior research. A separate review summarizes that absinthin activates TAS2R10, TAS2R14, TAS2R46, and TAS2R47 within the range of 0.1–100 µM. However, the description of absinthin in the primary study that served as the source has not yet been examined in detail.
In a receptor screening of oligopolynes isolated from the fungus Amaropostia stiptica, oligopolyne D activated TAS2R46 at a threshold concentration of 0.1 µM and was the lowest concentration at which any tested compound activated this receptor. The threshold for TAS2R1 for the same compound was 30 µM, making TAS2R46 approximately 300-fold more sensitive.
Within the scope of the abstract, caffeine triggers calcium signaling in TAS2R46-expressing cells, and the odor compound (R)-citronellal suppresses this response to a degree smaller than the inhibition observed in TAS2R43-expressing cells. No specific numerical value for the degree of inhibition is given in the abstract.
Sources for this overview
Checked for this overview: Broad responsiveness to sesquiterpene lactones and de-orphaning via harboside D / Caveat that high sensitivity is not evidence of selectivity due to broad responsiveness
Checked for this overview: Threshold and EC50 values for lactucopyrin and lactucin, and the description of highest sensitivity
IUPHAR/BPS Guide to PHARMACOLOGY: TAS2R46 (target 679) interaction records
Checked for this overview: Database registration of absinthin as a TAS2R46 agonist
Checked for this overview: Summary of activation of TAS2R10, 14, 46, and 47 in the 0.1–100 µM range
Checked for this overview: Threshold of 0.1 µM for oligopolyne D and TAS2R1 sensitivity comparison
Checked for this overview: Weak inhibition of caffeine response by citronellal
Follow the connections
lactucopicrin →activates→ TAS2R46
absinthin →activates→ TAS2R46
oligoporin D →activates→ TAS2R46
Measured values (2)
| Kind | Compound | Target | Value | Conditions | Source |
|---|---|---|---|---|---|
| receptor EC50 | lactucin | TAS2R46 | 8.85±1.17 µM | HEK293 cell assay | Lang R, 2022 |
| receptor EC50 | lactucopicrin | TAS2R46 | 0.35±0.06 µM | HEK293 cell assay | Lang R, 2022 |
Values are the reported values of each source (with units and conditions). Thresholds and EC50 depend on the panel and method; they are not single true values.
Structured claims — open a section to read each claim's confidence, evidence and limits
Mechanism and receptors (5)
Scope: Receptor assay in a cultured-cell system, in the cited study
Note: The same paper also reports overlapping receptor activation by other chicory lactones.
Show data
compound-lactucopicrin —activates→ receptor-tas2r46Scope: A curated and review-level summary of heterologous-expression receptor assays
Note: The individual values from the primary paper (Brockhoff 2007) are not in the abstract, and the full text has not been read. The gap between the receptor set given by the curation (46 only) and the review (10/14/46/47) is kept as is.
Show data
compound-absinthin —activates→ receptor-tas2r46Scope: Layer: cell. A screen using heterologous-expression cells for 26 human bitter taste receptors, with threshold concentrations measured by calcium imaging (Table 2).
Show data
compound-oligoporin-d —activates→ receptor-tas2r46Scope: Layer: cell. Cell functional experiments using several human bitter taste receptors reported to be caffeine-sensitive.
Note: Suess et al. 2018's full text was not reached because of a subscription restriction; confirmed from an OpenAlex abstract restoration.
Show data
compound-caffeine —activates→ receptor-tas2r46Scope: Layer: literature. A computational (molecular docking) prediction, not a cell or sensory experiment. A molecular docking simulation of tangeretin, nobiletin, and amarogentin (with strychnine separately as a positive control) against the cryo-EM structure of the human bitter taste receptor T2R46 (PDB 7XP6).
Note: Preliminary because this is a computational docking prediction, not confirmation of functional receptor activation by a cell assay or similar. The statement that tangeretin and nobiletin activate T2R46 in vitro is a citation of Kuroda et al. 2016 (a secondary citation), but the binding-energy values themselves are primary data from this paper's own docking calculations.
Show data
compound-pmfs —is_reported_to_activate→ receptor-tas2r46