Twenty-Five Bitter Taste Receptors: What Do They Divide Between Them?
Bitterness is not received by a single sensor. The taste cells on the tongue carry a family of receptors called TAS2R, and in one study's heterologous-expression screen, 25 human receptors were expressed together and their responses to a large number of compounds were examined. This note follows what happens inside that number, 25 — receptors that respond broadly,receptors that answer to only a narrow range, and a single compound that moves multiple receptors at once — narrowing the focus to responses measured at the level of cultured cells.
Human bitter taste receptors are not a single sensor, and a review lays out a heterologous-expression screen that examines 25 of them together.
That there are receptors, such as TAS2R39 and TAS2R14, that respond broadly to many structurally different compounds has been confirmed in multiple cultured-cell assays.
Caffeine is reported to respond at 5 receptors, and it is recorded that even a person who lacks the gene for 1 of these still perceives its bitterness.
How closely the concentration that moves a receptor assay matches the concentration at which a person actually begins to perceive bitterness has not yet been sufficiently confirmed, compound by compound.
A family of receptors, and the number twenty-five
As a starting point, there is a review-level account holding that the sensation of bitterness itself is not mediated by a single molecule but, in part, by a family of receptors.
Note: Do not fix the receptor count without a current nomenclature source. / 2026-08-31: Calibration downgrade from established to supported, because the supporting evidence does not derive from a full-text check. Can be re-upgraded after a full-text check.
A review of human bitter taste receptors and their role in perception.
Limitations: An older review; the receptor nomenclature needs to be updated to current usage.
Verbatim: 'we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors.' The mouse T2R (mT2R-5) responds to cycloheximide, and human hT2R-4 and mouse mT2R-8 respond to denatonium and 6-n-propyl-2-thiouracil. A mouse strain with low sensitivity to cycloheximide carries an amino acid substitution in mT2R-5 that lowers receptor responsiveness, and tastant-dependent gustducin activation was demonstrated. Functional and genetic evidence, independent of the Meyerhof group, that TAS2R/T2R receptors mediate bitterness.
Limitations: Receptor-level and mouse-genetics evidence. The link to human perception rests on hT2R-4 responding to PROP/denatonium in vitro; the paper contains no human psychophysics.
What shows the scale of that family concretely is a heterologous-expression screen curated by IUPHAR/BPS's Guide to PHARMACOLOGY. Within this framework, which exposed 25 human bitter taste receptors to 104 compounds together, quinine is recorded as an agonist of TAS2R14, at a threshold of 10 uM.
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.
GtoPdb lists quinine as an Agonist of human TAS2R14, with assayDescription giving Threshold=10 uM and citing Meyerhof 2010 (PMID 20022913).
Limitations: Curation-level evidence. The primary full text could not be read in this survey. GtoPdb lists quinine only against TAS2R14 and TAS2R40, which appears to be a curated subset of the primary data.
The same quinine was also recorded, within the same screen, as an agonist of TAS2R40. Already at this point, a single compound does not have only one receiving receptor.
Among the receptors, there are what can be called 「広い」(in translation: "broad") types — ones that respond to many structurally different compounds. TAS2R39 shows a clear response to the galloylated forms of green-tea catechins (ECg and EGCg), while another study reports that it also responds broadly to a large set of structurally similar (iso)flavonoids.
Scope: A cultured-cell assay. A clear response to 300 uM ECg and EGCg. ECg is strongest, followed by EGCg, with EC and EGC far weaker
Note: The abstract reports only a single concentration (300 uM). The receptor is broadly tuned (many flavonoids also activate TAS2R39).
Cells expressing hTAS2R39 showed a clear response to 300 uM of both ECg and EGCg. Among the catechins tested, the response to ECg was strongest, followed by EGCg, with the responses to EC and EGC far weaker.
Limitations: The reported concentration is a single value (300 uM). This is an in vitro receptor response, not a direct measurement of bitterness.
Context: Of a large set of structurally related (iso)flavonoids, 70 activated hTAS2R39, with activation thresholds spanning 0.12-500 uM, showing the receptor's broad tuning. The abstract does not name individual tea catechins.
Limitations: Catechin-specific values are not visible at the abstract level. Used only as contextual information on tuning.
In an independent assay by the University of Porto and DIfE, (-)-epicatechin activated 3 receptors: TAS2R4, TAS2R5, and TAS2R39. This confirms, from a lab lineage independent of Narukawa 2011 (Shizuoka) and Roland 2013 (Wageningen), that a catechin-scaffold compound is an agonist of TAS2R39.
Limitations: Confirmed at abstract level only. The compound tested was the non-galloylated EC, not a re-measurement of ECg or EGCg themselves. EC50 is stated to vary 100-fold across compounds, but the value for EC is not given in the abstract.
Context: The primary full text of Narukawa 2011 has not been obtained, but the full-text Discussion of Roland 2013 (a different source), which independently re-tested the same receptor (hTAS2R39), directly quotes Narukawa's values: "Previously reported thresholds were between 10 and 30 µM for all four catechins (14)", and gives EC50 values of ECG 88.2 µM, EGCG 181.6 µM, EGC 395.5 µM, and EC 417.7 µM. Compared with Roland's own values (thresholds: ECG/EGCG 32 µM, EC 250 µM, EGC 500 µM; EC50: ECG 150.6 µM, EGCG 161.2 µM), it reports thresholds about 10 times higher for the non-galloylated catechins (EC and EGC), and explicitly notes the difference between assays.
Limitations: This line is a secondary citation from the full-text source record for Roland 2013 on TAS2R39 flavonoids, not from Narukawa 2011's own source record. It is not treated as a correction to Narukawa's own evidence row, but as supporting context drawn from a different source.
In a heterologous-expression receptor assay independent of Narukawa 2011 (a single concentration of 300 µM), dose-response thresholds and EC50 for 4 catechins against hTAS2R39 were quantified. Verbatim: "we identified thresholds of ECG, EGCG, EC, and EGC, to be 32, 32, 250, and 500 µM, respectively". EC50 was ECG 150.6 µM and EGCG 161.2 µM (EC and EGC could not be calculated). The ordering, in which the galloylated catechins (ECG, EGCG) have lower thresholds than the non-galloylated catechins (EC, EGC) -- meaning stronger activation -- is consistent with Narukawa.
Limitations: These are receptor-assay values, not a direct measurement of human sensory perception. Compared with Narukawa, thresholds about 10 times higher are reported for the non-galloylated catechins, so absolute values differ between assays (though the trend is the same).
TAS2R14 is a receptor known to be broader still: a pharmacophore-based virtual screen put forward 15 clinically used drugs as candidates, and activation was also confirmed in cultured-cell verification.
TAS2R1415 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) is activated in vitro by: preliminary
Scope: 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.
Molecular properties of known TAS2R14 agonists were incorporated into pharmacophore- and shape-based models, and further ligands were predicted computationally; in vitro testing by calcium imaging in TAS2R14-transfected HEK293 cells gave a prediction success rate of 30-80%, and 15 clinical drugs were found to activate TAS2R14. The hERG potassium channel emerged as an off-target common to these bitter drugs.
Limitations: Abstract only; the paper is not in PMC and the full text has not been obtained. Drug names, concentrations, potency, and whether a control screen against other TAS2Rs was run are not clear from the abstract. The 30-80% range is given without specifying which model or subset each end corresponds to.
Show datareceptor-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)"
Absinthin, the bitter principle of wormwood, likewise cannot be explained by a single receptor. GtoPdb's curation lists it as an agonist of TAS2R46, while another review summarizes it as activation spanning 4 receptors, TAS2R10, 14, 46, and 47.
Scope: 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.
Absinthin is listed as an agonist of TAS2R46 with affinity 5.0 (-log M). Source: PMID 17595105.
Limitations: A curation-level reading; the primary data have not been re-checked.
Context: hTAS2R46 was characterized as a receptor broadly responsive to sesquiterpene lactones (the abstract does not name absinthin explicitly as an individual compound).
Limitations: Individual results are in the full text and tables (not read).
Breadth has its limits, though. The catechins that broadly move TAS2R39 do not behave the same way toward TAS2R14. In the catechin table, epigallocatechin (EGC) alone did not activate TAS2R14. Even a broad receptor has partners it does not answer to.
Scope: A heterologous-expression cell receptor assay (cultured cells expressing hTAS2R14)
Verbatim: "We identified catechins as agonists of two bitter receptors, hTAS2R14 and hTAS2R39. Previously, only activation of hTAS2R39 was reported (14)." Compound table (hTAS2R14 column): (+)-catechin active (+), threshold 500 µM / EC weakly active (+/-), threshold 500 µM / ECG active (+), threshold 125 µM / EGC not active (-) / EGCG active (+), threshold 250 µM. EC50 could not be calculated for any of them (n.d.).
Limitations: EGC did not activate hTAS2R14 (-). Activation by EC was weak and uncertain (+/-). EC50 values could not be calculated (a limitation of the concentration range). This is a receptor assay, not a direct measurement of human sensory perception.
Conversely, there are also receptors that answer to only a narrow range. TAS2R1 responds to bitter dipeptides such as Gly-Phe and Gly-Leu, and to bitter tripeptides that activate it more strongly, and has been reported as the receptor activated by the greatest variety of peptides among those tested. The tasteless dipeptide Gly-Gly, on the other hand, did not move any hTAS2R even up to a high concentration of 100 mM.
Note: 2 independent lines of cell assay point to the same receptor. The contribution in vivo is not established.
The bitter dipeptides Gly-Phe and Gly-Leu (25 mM) activate hTAS2R1 most strongly, with no or weak response at other receptors. "the tasteless dipeptide, Gly-Gly, did not activate any hTAS2Rs." (tested up to 100 mM). "hTAS2R1 was more sensitive to bitter peptides than to other bitter compounds such as denatonium, picrotin, salicin, and caffeine."
Limitations: The authors state explicitly that background signal also rises at higher concentrations. This is a cell-assay result; the receptor's contribution in human sensory perception is not directly shown.
Bitter tripeptides activate T2R1 more strongly than dipeptides, with the strongest, Phe-Phe-Phe (FFF), having an EC50 in the micromolar range. Homology modeling places the bitter peptides binding to the same pocket on the receptor's extracellular face (a cap structure formed by TM1/2/3/7 and ECL1/2).
Limitations: The actual EC50 value is not given in the abstract. The modeling is not an experimental structure.
Statements: "TAS2R1 exhibited strong responses to the two bitter peptides GL and GF but not to the nonbitter GG" and "The receptor that was found to be activated by the highest number of peptides is the receptor TAS2R1." In Table 1 (List of Amino Acids/Peptides Activating Human Bitter Taste Receptors), the TAS2R1 row lists "F, GF, GL, IF, LW, FI, FL, WW, GLL, IQW, LKP, FFF, WWW, YPFPGPIHNS, LVYPFPGPIHN".
Limitations: Includes data integrated from prior literature (including Maehashi 2008 and Upadhyaya 2010); within the scope of extraction in this review, it has not been possible to fully separate out which data are this paper's own new experimental results.
The bitter fraction from a trypsin digest of casein is a mixture of many structurally different peptides. TAS2R1, TAS2R4, TAS2R14, and TAS2R16 all responded to this fraction, but TAS2R1 and TAS2R4 responded particularly strongly. Even within the same fraction, the division of labor is not uniform.
Note: The fraction is a mixture of numerous peptides; the correspondence between individual peptides and receptors cannot be identified from this experiment alone (see limits).
Cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 respond to bitter fraction M (2.5 mg/mL, "tastes moderately bitter (equivalent to the bitterness of 0.125 mM of quinine)"), obtained by gel filtration of a 12-hour trypsin digest of casein (1%), with hTAS2R1 and hTAS2R4 responding especially strongly.
Limitations: The fraction is a mixture; the response is attributable only at the level of the fraction.
Limits: The authors state explicitly that the bitter fraction contains numerous structurally different peptides and is likely to include non-bitter peptides as well. In addition, background signal rises at high peptide concentrations, and hTAS2R16 showed no significant response to the synthetic dipeptides (though it did respond to its specific ligand, salicin).
Limitations: The correspondence between individual peptides and individual hTAS2Rs cannot be established with this experimental system.
A narrower division still is seen in an exhaustive screen that exposed 34 mouse receptors to 128 natural bitter compounds. Theobromine, found in cacao, had a threshold concentration in only a single column, Tas2r121, with every other column left blank. This is a mouse receptor, not a human result.
Scope: A heterologous-expression screen of 34 mouse Tas2r receptors against 128 mostly natural bitter compounds
Note: A non-human receptor. A single study, single value; no EC50 for theobromine has been found.
In Table 1, entitled "Threshold concentrations (mm) for Tas2r activators", the theobromine row has a single value, 0.03, in the Tas2r121 column, and every other column is a dash.
Limitations: A mouse receptor, not human. That the Table 1 columns are mouse Tas2r numbers only has been verified twice on a focused re-read. No EC50 for theobromine is given.
TAS2R50 was for a long time a 「オーファン受容体」(in translation: "orphan receptor") — one with no known partner it responded to. It is an example where a partner was found for the first time only once 2 compounds, andrographolide and amarogentin, were identified as agonists.
Scope: A receptor assay in a heterologous expression system (cultured cells)
Note: GtoPdb also lists amarogentin as an agonist of TAS2R46 (affinity 4.2, PMID 26406243). The TAS2R46 side is kept here in these notes rather than made a separate claim (because the primary paper has not been read).
Identified the natural bitter terpenoids andrographolide and amarogentin as agonists of hTAS2R50, and pharmacologically characterized the receptor.
Limitations: Read at abstract level. EC50 and threshold values are not claimed, as the full text has not been read.
TAS2R16 is likewise a receptor with a narrow post, responding to bitter glycosides such as salicin. Its response has been reported to be competitively inhibited, respectively, by 3 umami-related substances: monosodium glutamate (MSG), inosinic acid (IMP), and L-theanine. Different substances are pushing back against the same narrow post in the same way.
Adding IMP raised salicin's EC50 by 2-3 fold, and at the highest concentration (IMP 30 mM) the maximal response to salicin alone decreased by 50%. Verbatim: "the maximal response of salicin alone was gradually decreased by... 50%... at the highest concentration of... IMP (30 mM)".
Limitations: The abstract gave only the qualitative classification "partial insurmountable antagonist", but the full text confirmed quantitative values — the percentage decrease in maximal response and the fold shift in EC50. Not a human sensory test.
At the highest concentration of L-theanine (100 mM), the maximal response to salicin alone decreased by 55%, and the EC50 rose 2-3 fold. Verbatim: "the maximal response of salicin alone was gradually decreased by 61%, 50%, and 55% at the highest concentration of Glu-Glu (10 mM), IMP (30 mM), and l-theanine (100 mM), respectively".
Limitations: Not a human sensory test. Whether this effect occurs at the concentrations of theanine found in tea infusions is outside the scope of this study.
Caffeine's bitterness is not the work of a single receptor. In cultured-cell assays, 5 receptors — hTAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 — have been reported to respond to caffeine.
The abstract of an independent functional calcium-imaging study explicitly states, as background, "caffeine, which activates five human bitter taste receptors" (a restatement of the Meyerhof-lineage finding). In that study's own assay as well, TAS2R43/46 responded to caffeine (less sensitively than to mozambioside). This shows that the attribution of 5 receptors was still maintained as a premise in the research community as of 2020.
Limitations: The names of the 5 receptors (TAS2R7/10/14/43/46) are not listed in the abstract. The primary data are Meyerhof 2010 (the related record; full text not reached), and this row remains a restatement plus partial (TAS2R43/46) direct confirmation. The author list includes Behrens and is not independent of the Meyerhof lineage.
This division of labor comes with redundancy. People who lack the TAS2R43 gene make up about 18-30% of the population, yet caffeine's bitterness is still perceived. Even lacking 1 of the 5 receiving receptors, the remaining ones can be regarded as taking on caffeine.
caffeine remains bitter even for people lacking TAS2R43supported
Scope: The correspondence between the frequency of the gene deletion in human populations and perception
Note: An example that a single receptor cannot explain bitterness perception. "About 18-30%" is a review-level figure. Note that the primary data (946 people / 52 populations) give a deletion-allele frequency of 0.33, a different kind of quantity from "the proportion of individuals lacking the gene".
About 18-30% of the population lacks the TAS2R43 gene, yet caffeine's bitterness is perceived.
Limitations: Via a review. The primary source for the deletion frequency is not included.
Context: Gives the population-genetic basis underlying this claim from primary data rather than via a review: in 946 subjects from 52 populations worldwide, copy number for both TAS2R43 and TAS2R45 ranged from 0 to 2, and the 43delta and 45delta deletions occurred at high frequency worldwide (0.33 and 0.18). The TAS2R43 deletion spans 37.8 kb, including the entire coding region, and the paper states that in Europe more than 20% of subjects lacked this gene. No signal of natural selection was found, and the authors attribute this pattern to genetic drift.
Limitations: What this study measures is gene copy number, not caffeine perception, so the study itself does not show that caffeine remains bitter in the absence of TAS2R43. It also refines the figure carried over by the review: the reported quantity is a deletion-allele frequency of 0.33, which is not the same as the proportion of people lacking the gene; the paper gives a regional figure for Europe (more than 20%) rather than a single worldwide percentage. The 18-30% range recorded from Poole 2017 should therefore be treated as a review-level approximation.
Hop-derived bitter compounds likewise divide their receiving receptors according to structure. Stereoisomers of the iso-α-acids and compounds such as 8-prenylnaringenin have been reported to activate 3 receptors: TAS2R1, TAS2R14, and TAS2R40.
Scope: Hop-derived bitter compounds including iso-α-acid stereoisomers, α-acids, and 8-prenylnaringenin
Note: Recorded from a structural bioinformatics paper that restates the attribution to the 3 receptors as established prior knowledge. The underlying receptor-assay source (Intelmann et al. 2009, Chemosensory Perception) could not be obtained in abstract or full text and is listed as metadata_only in sources.csv. Per-receptor entities (receptor-tas2r1 / tas2r14 / tas2r40) have deliberately not been created until the assay-level source can be read.
The abstract states that the bitterness of hop-derived compounds was found to be mediated by 3 bitter taste receptors, TAS2R1, TAS2R14, and TAS2R40, and reports a structural bioinformatics characterization of the binding modes of trans-/cis-isocohumulone, -isohumulone, -isoadhumulone, cohumulone, humulone, adhumulone, and 8-prenylnaringenin at the orthosteric binding sites of these receptors. A conserved asparagine in transmembrane helix 3 is essential for recognizing hop-derived compounds, and the surrounding binding-site residues determine ligand specificity.
Limitations: The attribution to the 3 receptors is presented as established prior knowledge rather than a new measurement in this paper, and the abstract reports no cell-based receptor assay. The underlying primary assay literature (Intelmann et al. 2009, Chemosensory Perception, DOI 10.1007/s12078-009-9049-1) could not be read in this survey and is registered as metadata_only. The docking results are computational predictions, not measured activation.
Plasmids encoding 25 human TAS2Rs were transiently expressed in HEK293T cells and stimulated with 15 hop-derived compounds including α-acids, β-acids, trans/cis-iso-α-acids, isoxanthohumol, xanthohumol, and 8-prenylnaringenin. Depending on chemical structure, these activated hTAS2R1, hTAS2R14, and hTAS2R40.
Limits: The threshold concentrations and EC50 values obtained from the receptor assay were far lower than the values determined in human psychophysical experiments. However, the rank order of potency across compounds was similar between the two experiments.
Limitations: Abstract checked only. This limitation guards against treating the in vitro threshold as a human perceptual threshold.
The same receptor works with different partners in different settings
TAS2R31 is a receptor that keeps turning up in front of a different partner. In one study, people carrying a particular TAS2R31 variant rated quinine's bitterness lower, while, in the same subject population of the same study, they also showed higher recalled liking for grapefruit juice — 2 separate judgments tied to the same variant.
Scope: 246 adults (mostly of European ancestry). Recalled liking of unsweetened grapefruit juice was rated on a bipolar hedonic scale
Note: A parallel association was seen with quinine bitterness (21.5 versus 30.8 gLMS). The authors discuss the possibility that the earlier TAS2R19 association reflects linkage disequilibrium with TAS2R31. The verified agonist of TAS2R31 is quinine, not naringin or limonin.
Val240 homozygotes rated quinine's bitterness lower (21.5 plus-minus 1.9; Ile240 homozygotes rated it 30.8 plus-minus 3.1), and had higher remembered liking for grapefruit juice (9.3 plus-minus 4.5 versus -16.53 plus-minus 7.1). 3 SNPs at TAS2R19/TAS2R31 form a haplotype block (D' of 0.96 and 0.87), and the earlier TAS2R19 association may be an LD artifact.
Limitations: Grapefruit liking is based on memory, not actual tasting. The SNP is a tag SNP rather than the putative causal variant Arg35Trp, and may be in LD with an unmeasured variant (a limitation the authors themselves note).
Context: The presence of high LD spanning functionally distinct TAS2R loci predicts that bitterness responses to many compounds will correlate strongly even when mediated by different genes. Haplotype analysis showed that most single-marker associations in the TAS2R30-46 cluster are an apparent product of LD with TAS2R31.
Limitations: This provides mechanistic background for Hayes 2015's argument that the earlier TAS2R19-grapefruit/quinine association may be an LD artifact of TAS2R31; the study itself does not test grapefruit liking.
For individual variation in the bitter aftertaste of saccharin and acesulfame K as well, genetic and functional analysis showed that TAS2R31 is the actual bearer. Once the strong linkage disequilibrium with neighboring receptor genes was untangled, most of the apparent associations turned out to be apparent effects arising from linkage with TAS2R31.
TAS2R31 mediates individual variation in the bitterness of saccharinsupported
Scope: Full-gene sequencing of TAS2R30-46 in 60 white subjects, taste responses to both sweeteners, and in vitro assays of receptor alleles. 30 markers were initially associated at P < 0.001
Thirty markers, including non-synonymous variants across all 5 TAS2R30-46 genes, were associated with the response to saccharin and acesulfame K (P < 0.001), but linkage disequilibrium in this region is high (D prime and r2 > 0.95), and haplotype analysis showed that most of the association is apparent, arising from LD with TAS2R31 variants. The in vitro assay confirmed the functional importance of 4 TAS2R31 variants that have independent effects on receptor response.
Limitations: Abstract level: identification of the 4 TAS2R31 variants and their effect sizes are in the full text, which has not been obtained. A sample from a single ancestral population.
The division of labor can also be seen from the side that stops a response. The small molecule GIV3727 inhibits 6 receptors, including TAS2R31, while it did not inhibit the remaining receptors tested in the same panel. Not only the side that moves a receptor, but the side that stops it, has its own receptor-by-receptor post.
Scope: Calcium imaging in HEK293 cells stably or transiently expressing a single hTAS2R together with the chimeric G protein G16gust44. The panel screen tested antagonists at 25 uM
Note: Identified from a screen of 17,854 compounds, which yielded 139 candidate antagonists. The authors conclude it is most likely an orthosteric, non-surmountable antagonist: 25 uM GIV3727 shifted the agonist EC50 by 3- to 10-fold and reduced the maximal signal amplitude by 35-70%.
A high-throughput calcium-imaging screen of 17,854 compounds against hTAS2R31 yielded 139 candidate antagonists, of which GIV3727 showed an IC50 of 6.4 +/- 2.4 uM against acesulfame K and 7.9 +/- 6.1 uM against saccharin (n = 3). Inhibition was reversible by washing. Tested at 25 uM against 18 of the 25 hTAS2Rs with known agonists, GIV3727 significantly inhibited 6 receptors (hTAS2R4, 7, 40, 43, 31, 20) and did not inhibit the rest. Mutagenesis showed that a basic residue at position 7.39 (Lys265) is a key contact point in the hTAS2R46 scaffold.
Limitations: For 4 receptors (hTAS2R3/5/7/13), an accurate EC90 agonist concentration could not be established, and the maximal agonist concentration that did not produce artifacts was used instead, so inhibition of hTAS2R7 at the true EC90 is uncertain. The lysine at position 7.39 is not a sufficient condition for sensitivity: hTAS2R50 also has the same residue but is not sensitive.
Source: Modulation of bitter taste perception by a small molecule hTAS2R antagonist (Slack JP; Brockhoff A; Batram C; Menzel S; Sonnabend C; Born S; Galindo MM; Kohl S; Thalmann S; Ostopovici-Halip L; Simons CT; Ungureanu I; Duineveld K; Bologa CG; Behrens M; Furrer S; Oprea TI; Meyerhof W, 2010) · full text checked
Show datacompound-giv3727 —antagonizes→ receptor-tas2r31
Most of the results lined up here are calcium responses or reporter responses in cultured cells with a receptor artificially expressed. In the body text and cards we keep the source material's own words, 「応答する」(in translation: "to respond") and 「活性化する」(in translation: "to activate"), as they are, and do not write a cell's response as a paraphrase for the sensation 「苦い」(in translation: "bitter").
The relationship between theobromine and Tas2r121 is via a mouse receptor, and cannot be carried over to humans as is.
The effects on TAS2R14's 15 clinical drugs, TAS2R50's amarogentin, and some of GIV3727's receptors include ones that remain confirmed only at the abstract stage.
The genetic story of the receptor behind individual variation in sensitivity to phenylthiocarbamide and propylthiouracil is treated separately, focused on that one receptor alone, and is not touched on here.
Frequently asked
How many sensors does the body have for perceiving bitterness?
One heterologous-expression screen expresses 25 human bitter taste receptors together and examines their response to a large number of compounds. Bitterness is not a single sensor, and a review lays out that it is mediated in part by this family of 25 receptors. However, how many receptors are not included in this screen, or how many still have no agonist found for them, cannot be counted within the scope of this ledger. The correspondence between the number of receptors and how much of an actual food's bitterness they can explain also remains, for now, a matter that must be confirmed individually, compound by compound.
Is caffeine's bitterness perceived through a single receptor?
In assays using cultured cells, caffeine is reported to respond at 5 receptors: TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46. This division of labor carries redundancy: people who lack the TAS2R43 gene make up roughly 18 to 30% of the population, yet it is reported that they still perceive caffeine's bitterness. This can be taken as a result in which the remaining receptors take on caffeine, but no material has been found within this ledger that separates out, individually, how much each of the 5 receptors actually contributes to perception.
What is not known
How much the concentration that moves a receptor assay differs from the concentration at which a person actually begins to perceive bitterness cannot be known without checking compound by compound, and there is not yet a correspondence table spanning this whole ledger.
No material has been found that directly examined how the multiple judgments involving TAS2R31 (quinine's rating, the aftertaste of saccharin and acesulfame K, and liking for grapefruit) move together within the same person.
Of the total of 25 receptors, this ledger does not include material that counts up how many of them actually have an agonist found for them on the human tongue.
Whether a human receptor exists corresponding to the theobromine-Tas2r121 relationship found in mice has not been confirmed.