ArticleThe Journal of biological chemistry2014
Amino acid derivatives as bitter taste receptor (T2R) blockers.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 98 citations in OpenAlex.
- Bitter Compounds in Medicinal Food Plants Based on Traditional Chinese Medicine: Analysis and Regulation Strategies from Chemical Structure to Perception Mechanisms.Molecules (Basel, Switzerland) · 2026Review
- Saltiness and Bitterness Perception of KCl-Based Mixed Salts (KCl/NaCl/L-Arginine) Evaluated by the R-Index and Partial Projective Mapping Methods.Foods (Basel, Switzerland) · 2026Article
- Severe Hypoxia Reduces Adenylyl Cyclase 6 Expression and Function in Bronchial Epithelial Cells.FASEB bioAdvances · 2026Article
- Beef-Derived Peptides Mediated Desensitization of Bitter Taste Receptor T2R14 Through GPCR Kinase 2.Nutrients · 2026Article
- Article
- Preparation, Separation, and Identification of Low-Bitter ACE-Inhibitory Peptides from Sesame (Foods (Basel, Switzerland) · 2026Article
- Effect of Phenolic Compounds and Terpenes on the Flavour and Functionality of Plant-Based Foods.Nutrients · 2025Review
- Development of Palatable Amorphous Trazodone Hydrochloride Formulations via Ion Exchange.Pharmaceutics · 2025Article
- From Sweetness to Mouthfeel: A Review on Overcoming Sensory Barriers in Sugar-Free Beverages.International journal of food science · 2025Review
- Bitter taste receptor T2R14-Gαi coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis.iScience · 2024Article
- Potential of Bitter Medicinal Plants: A Review of Flavor Physiology.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Thiazolidinediones are Partially Effective Bitter Blockers.Clinical therapeutics · 2024Article
- Article
- Interkingdom Detection of Bacterial Quorum-Sensing Molecules by Mammalian Taste Receptors.Microorganisms · 2023Review
- Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.Chemical senses · 2023Article
- Extraoral expression and characterization of bitter taste receptors inFASEB bioAdvances · 2022Article
- BitterMatch: recommendation systems for matching molecules with bitter taste receptors.Journal of cheminformatics · 2022Article
- Pharmacology of T2R Mediated Host-Microbe Interactions.Handbook of experimental pharmacology · 2022Article
- Bitter Taste Receptors in the Airway Cells Functions.Handbook of experimental pharmacology · 2022Article
- Functional molecular switches of mammalian G protein-coupled bitter-taste receptors.Cellular and molecular life sciences : CMLS · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In humans, the 25 bitter taste receptors (T2Rs) are activated by hundreds of structurally diverse bitter compounds. However, only five antagonists or bitter blockers are known. In this study, using molecular modeling guided site-directed mutagenesis, we elucidated the ligand-binding pocket of T2R4. We found seven amino acids located in the extracellular side of transmembrane 3 (TM3), TM4, extracellular loop 2 (ECL2), and ECL3 to be involved in T2R4 binding to its agonist quinine. ECL2 residues Asn-173 and Thr-174 are essential for quinine binding. Guided by a molecular model of T2R4, a number of amino acid derivatives were screened for their ability to bind to T2R4. These predictions were tested by calcium imaging assays that led to identification of γ-aminobutryic acid (GABA) and Nα,Nα-bis(carboxymethyl)-L-lysine (BCML) as competitive inhibitors of quinine-activated T2R4 with an IC50 of 3.2 ± 0.3 μM and 59 ± 18 nM, respectively. Interestingly, pharmacological characterization using a constitutively active mutant of T2R4 reveals that GABA acts as an antagonist, whereas BCML acts as an inverse agonist on T2R4. Site-directed mutagenesis confirms that the two novel bitter blockers share the same orthosteric site as the agonist quinine. The signature residues Ala-90 and Lys-270 play important roles in interacting with BCML and GABA, respectively. This is the first report to characterize a T2R endogenous antagonist and an inverse agonist. The novel bitter blockers will facilitate physiological studies focused on understanding the roles of T2Rs in extraoral tissues.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.