human TAS2R receptor family
receptor / receptor-tas2r-family
ヒトTAS2R受容体ファミリー
Family of G-protein-coupled receptors involved in human bitter taste detection. Expressed also in tissues outside the tongue (airways, paranasal sinuses, intestines), where they participate in cell-autonomous chemical sensing independent of taste perception (the physiological ligands and detection methods for extraoral function remain disputed).
On this page (6 sections)
Reading the bitterness
The human TAS2R receptor family comprises a group of G-protein-coupled receptors that detect bitter compounds in taste buds of the tongue. In experiments expressing mouse and human receptors in heterologous cells, the mouse receptor mT2R-5 responded to cycloheximide, and human hT2R-4 and mouse mT2R-8 responded to denatonium and propylthiouracil. A mouse strain with low sensitivity to bitter compounds showed amino acid substitutions in mT2R-5 that reduced receptor responsiveness. This receptor-level and mouse genetic evidence forms the foundation for understanding that the TAS2R family mediates bitter taste.
It is not uncommon for a single bitter compound to activate multiple TAS2R receptors simultaneously, or for a single receptor to respond to multiple bitter compounds. In receptor assays using cultured cells, caffeine is reported to activate 5 receptors (hTAS2R7, 10, 14, 43, 46), while hop-derived bitter compounds (iso-alpha-acids and prenyl naringenin, among others) activate 3 receptors (TAS2R1, 14, 40). In a bitter fraction from trypsin-digested casein, cells expressing hTAS2R1, 4, 14, 16 responded, with hTAS2R1 and hTAS2R4 showing particularly strong responses. However, this fraction is a mixture of numerous peptides, and individual peptide-receptor correspondences have not been determined.
TAS2R is not exclusively a receptor of the tongue. In experiments using cultured human airway epithelium, motile cilia were found to express T2R4, T2R43, T2R38, T2R46, and addition of bitter compounds elevated intracellular calcium, increasing ciliary beat frequency by approximately 25%. In airway smooth muscle, bitter compounds such as quinine relax muscle far more strongly than the β-agonist isoproterenol; in one experiment, active tension was lost by >90%, whereas isoproterenol resulted in only approximately 30% reduction. However, chloroquine and denatonium used in these experiments required high concentrations (approximately 100 µM) to completely relax pre-contracted muscle, and the authors themselves note the possibility that these are not ideal candidates for clinical application. Although this relaxation was reproduced in another laboratory, explanations conflict between those proposing that local calcium elevation opens potassium channels and those proposing the opposite—that it inhibits those channels and blocks calcium channels—and the mechanism remains unsettled.
What extraoral TAS2Rs originally detect in the body remains, in most cases, unknown. Researchers in this field themselves point out that the majority of bitter compounds used in experiments are not the physiological ligands that these receptors encounter naturally. A rare exception is airway T2R38, which has been shown to respond to quorum-sensing molecules (acyl-homoserine lactones) produced by Pseudomonas aeruginosa and other bacteria, confirmed in human paranasal sinus cultures from genotyped subjects. These molecules are considered to be natural ligands that the paranasal sinus epithelium actually encounters, not food-derived bitter compounds. This single example demonstrates that natural ligands may be found for extraoral TAS2Rs, but this finding does not extend broadly to other tissues.
Sources for this overview
T2Rs function as bitter taste receptors
Checked for this overview: Confirmed in the main text: receptor function identification of mouse mT2R-5 and human hT2R-4.
Checked for this overview: Confirmed in the main text: the number of 5 receptors activated by caffeine.
In Silico Investigation of Bitter Hop-Derived Compounds and Their Cognate Bitter Taste Receptors
Checked for this overview: Confirmed in the main text: the 3 receptors activated by hop bitter compounds.
Bitter peptides activate hTAS2Rs, the human bitter receptors
Checked for this overview: Confirmed in the main text: response of 4 receptors to the casein digest fraction. / Confirmed in the main text: bitter fraction is a mixture with unclear correspondences.
Motile cilia of human airway epithelia are chemosensory
Checked for this overview: Confirmed in the main text: receptor expression in airway cilia and the approximately 25% increase in beat frequency.
Checked for this overview: Confirmed in the main text: the value of >90% relaxation of airway smooth muscle by bitter compounds.
The cellular and molecular basis of bitter tastant-induced bronchodilation
Checked for this overview: Confirmed in the main text: airway smooth muscle relaxation independently reproduced. / Confirmed in the main text: that explanations of the mechanism conflict regarding potassium channels. / Confirmed in the main text: high concentration needed for complete relaxation; non-ideal possibility. / Confirmed in the main text: the researchers' note that experimental bitter compounds may not be physiological ligands.
Extraoral bitter taste receptors in health and disease
Checked for this overview: Confirmed in the main text: the assessment that physiological ligands for extraoral T2Rs remain unestablished.
T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
Checked for this overview: Confirmed in the main text: the exception that T2R38 responds to bacterial acyl-homoserine lactones (AHLs).
Follow the connections
bitterness →is mediated in part by→ human TAS2R receptor family
caffeine →activates→ human TAS2R receptor family
hop bitter acids →is reported to activate→ human TAS2R receptor family
Structured claims — open a section to read each claim's confidence, evidence and limits
Mechanism and receptors (10)
Scope: Human oral bitterness perception
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.
Show data
sensation-bitter —is_mediated_in_part_by→ receptor-tas2r-familyScope: A receptor assay in a cultured-cell system (Meyerhof et al.'s results as cited by a review)
Note: EC50 is not given in the review.
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compound-caffeine —activates→ receptor-tas2r-familyScope: 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.
Show data
compound-hop-bitter-acids —is_reported_to_activate→ receptor-tas2r-familyScope: HEK293 heterologous expression, calcium imaging
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).
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compound-class-bitter-peptides —activates_multiple_members_of→ receptor-tas2r-familyScope: Cultured primary human airway epithelium. The response is cell-autonomous within epithelial cells and does not involve taste nerves or taste perception.
Note: Detection was by microarray, RT-PCR, and anti-T2R immunofluorescence. The precise molar concentration of bitter compounds could not be confirmed verbatim in the second pass and is therefore not recorded here. Single laboratory; the paper does not include human in vivo mucociliary clearance measurements.
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receptor-tas2r-family —is_expressed_on→ "Motile cilia of human airway epithelial cells (with T2R4, T2R43, T2R38, T2R46 identified). Bitter compounds elevate intracellular calcium and increase ciliary beat frequency by approximately 25% (N = 4, P < 0.01)."Scope: Human airway smooth muscle cells and ex vivo intact airways, as well as mouse in vivo airway resistance (with aerosolized quinine inhalation, airway resistance decreased by 53 +/- 2.96% in normal mice and 50 +/- 8% in ovalbumin-sensitized mice).
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receptor-tas2r-family —mediates→ "Relaxation of airway smooth muscle and bronchodilation of intact airways approximately 3-fold greater than β-agonists (bitter compounds: loss of active tension >90% maximum; isoproterenol under the same conditions: 30 +/- 9.2% reduction)."Scope: Cultured human airway smooth muscle cells (Deshpande 2010) versus freshly isolated mouse and human native airway smooth muscle cells and tissue (Zhang 2013).
Note: Deshpande 2010 proposes local Ca2+ and BKCa activation. Zhang 2013 reports no detectable local Ca2+ events in any of 14 native cells, and that bitter compounds inhibit rather than activate BKCa channels, with 3 different BKCa channel blockers each failing to affect bronchodilation by bitter compounds; they instead propose inhibition of L-type voltage-dependent Ca2+ channels via Gβγ. The two studies differ in species and sample preparation (cultured versus freshly isolated), which itself is a candidate explanation for the discrepancy.
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receptor-tas2r-family —induces_bronchodilation_via→ "Local intracellular calcium signals at the cell membrane. Opens large-conductance calcium-activated potassium (BKCa) channels, causing hyperpolarization of airway smooth muscle."Scope: The current state of the field as described by two independent groups that wrote about airway smooth muscle and extraoral T2Rs in general.
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receptor-tas2r-family —has_unresolved_property→ "The physiological ligands for extraoral TAS2Rs remain largely unidentified, and the bitter compounds used in experiments are not endogenous ligands."Scope: Methodological assessment of extraoral T2R literature in a review by an active research laboratory in the field.
Note: Recorded to correctly discount expression-only claims regarding extraoral TAS2Rs. The same review notes that while α-gustducin and TRPM5 have been detected in serotonin-producing and GLP-1-producing cells, no immunostaining evidence exists for colocalization of enteroendocrine cell markers and T2Rs.
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receptor-tas2r-family —has_methodological_limitation→ "Expression profiling of extraoral TAS2Rs relies primarily on in situ hybridization and RT-PCR because well-validated T2R antibodies are unavailable. Additionally, because TAS2R genes lack introns and extraoral expression is extremely low, incomplete removal of genomic DNA compromises the reliability of the obtained expression profile."Scope: Mouse stomach. Intragastric T2R agonist administration to wild-type, α-gustducin-knockout, and ghrelin receptor-knockout mice.
Note: Rodents only. After an initial transient increase in feeding in the first 30 minutes, a prolonged decrease correlated with gastric emptying inhibition continues over the subsequent 4 hours, so the direction of the appetite effect is time-dependent and must not be summarized simply as appetite suppression. Extracted at the abstract level.
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receptor-tas2r-family —regulates→ "Mouse gastric ghrelin secretion, short-term feeding intake, gastric emptying. Partially mediated via α-gustducin: oral administration of T2R agonists increased plasma octanoyl ghrelin in wild-type mice, but the effect was partially attenuated in gustducin-knockout mice."