Bitter Taste Receptors Research Articles

Bioelectronic Tongue for Identifying and Masking Bitterness Based on Bitter Taste Receptor Agonism and Antagonism

AbstractBitterness elicits unpleasant sensations in humans, which can hinder the acceptance of foods and medication adherence. Therefore, identifying and masking bitter tastes is crucial for developing palatable foods and promoting medication compliance in the food and pharmaceutical industries. To achieve this, employing agonism and antagonism of bitter taste receptors as effective strategies at the molecular level is essential. In this study, a bioelectronic tongue is developed to characterize the agonism and antagonism of bitter taste receptors. The human bitter taste receptors hTAS2R16 and hTAS2R31 are produced using an Escherichia coli expression system and reconstituted into nanodiscs (NDs). Subsequently, hTAS2R16‐ and hTAS2R31‐NDs are immobilized on the surface of graphene field‐effect transistors (FETs) to construct bioelectronic tongues. The developed system sensitively detected the bitter agonists, salicin and saccharin, at concentrations as low as 100 fM, with high selectivity in real‐time. The dose‐dependent curves shifted and K values decreased by the antagonists of hTAS2R16 and hTAS2R31, indicating antagonism‐based masking of bitter taste. Therefore, the developed bioelectronic tongue holds promise for identifying bitter tastes and evaluating the masking of bitterness based on the agonism and antagonism of hTAS2Rs.

Pathophysiological features of chronic IgE-mediated rhinosinusitis of bacterial etiology

Chronic rhinosinusitis (CRS) is a disease caused by inflammation of the paranasal sinuses and its mucous membrane lasting for more than 4 weeks continuously. The aim of our study was to examine the main pathophysiological features of chronic IgE-mediated rhinosinusitis of bacterial etiology according to publications in the Russian Federation and in the world. A search was made through English- and Russian-language literature sources using the following databases: PubMed, MedLine, Web of Science, Russian Science Citation Index, Springer, Scopus, Scientific Research, Google Scholar, Crossref, eLibrary. The epidemiological features of CRS in the Russian Federation, bacterial pathogens and pathophysiological characteristics of CRS were analyzed. A 2-fold increase in the prevalence of CRS was registered over the past 20 years. Prevalence of the disease increases at longer age ranges. Chronic rhinosinusitis ranks first among all chronic diseases in the field of otorhinolaryngology. Allergic rhinitis, asthma, bronchiectasia, immunodeficiencies, cystic fibrosis, primary ciliary dyskinesia and autoimmune diseases are associated with CRS. The most common bacterial pathogens are S. aureus, Staphylococcus epidermidis and Propionibacterium acnes, Prevotella, Streptococcus and Veillonella, and some Gram-negative bacteria, e.g., Pseudomonas aeruginosa (P. aeruginosa), Proteus mirabilis and Klebsiella pneumoniae. Staphylococcus aureus (S. aureus) is involved in pathogenesis of nasal polyps. The colonizing bacteria may contribute to pathogenesis of CRS through the formation of biofilms. Alterations in the sino-nasal microbiome may also contribute to the development of CRS. An association of the CRS and CFTR gene mutations plays a significant role in the pathogenesis of chronic rhinosinusitis. An “immune barrier hypothesis” has been proposed as potential mechanism of CRS. Reduced expression of SPINK5, impaired STAT3 signaling, and T2R38 bitter taste receptor polymorphism have been identified in the pathogenesis of CRS. The T2R38 gene stimulates epithelial cells to produce nitrous oxide with a bactericidal effect, promotes mucociliary elimination of pathogens and prevention of upper respiratory tract infections, the polymorphism of this gene predisposes patients to gram-negative infectious diseases, and therefore is a risk factor for the development of CRS. In addition, antibody deficiency is the most common primary immunodeficiency associated with CRS.Hence, the pathogenesis of chronic IgE-mediated rhinosinusitis of bacterial etiology is associated with defects in innate immunity and mucociliary clearance, influence of the sinonasal microbiome, allergies, and genetic factors. A comprehensive assessment of these factors is necessary for the development of new preventive and therapeutic options for the correction of CRS.

Bitter taste receptor (TAS2R) 46 in human skeletal muscle: expression and activity.

Bitter taste receptors are involved not only in taste perception but in various physiological functions as their anatomical location is not restricted to the gustatory system. We previously demonstrated expression and activity of the subtype hTAS2R46 in human airway smooth muscle and broncho-epithelial cells, and here we show its expression and functionality in human skeletal muscle cells. Three different cellular models were used: micro-dissected human skeletal tissues, human myoblasts/myotubes and human skeletal muscle cells differentiated from urine stem cells of healthy donors. We used qPCR, immunohistochemistry and immunofluorescence analysis to evaluate gene and protein hTAS2R46 expression. In order to explore receptor activity, cells were incubated with the specific bitter ligands absinthin and 3ß-hydroxydihydrocostunolide, and calcium oscillation and relaxation were evaluated by calcium imaging and collagen assay, respectively, after a cholinergic stimulus. We show, for the first time, experimentally the presence and functionality of a type 2 bitter receptor in human skeletal muscle cells. Given the tendentially protective role of the bitter receptors starting from the oral cavity and following also in the other ectopic sites, and given its expression already at the myoblast level, we hypothesize that the bitter receptor can play an important role in the development, maintenance and in the protection of muscle tissue functions.

The avian taste system.

Taste or gustation is the sense evolving from the chemo-sensory system present in the oral cavity of avian species, which evolved to evaluate the nutritional value of foods by detecting relevant compounds including amino acids and peptides, carbohydrates, lipids, calcium, salts, and toxic or anti-nutritional compounds. In birds compared to mammals, due to the relatively low retention time of food in the oral cavity, the lack of taste papillae in the tongue, and an extremely limited secretion of saliva, the relevance of the avian taste system has been historically undermined. However, in recent years, novel data has emerged, facilitated partially by the advent of the genomic era, evidencing that the taste system is as crucial to avian species as is to mammals. Despite many similarities, there are also fundamental differences between avian and mammalian taste systems in terms of anatomy, distribution of taste buds, and the nature and molecular structure of taste receptors. Generally, birds have smaller oral cavities and a lower number of taste buds compared to mammals, and their distribution in the oral cavity appears to follow the swallowing pattern of foods. In addition, differences between bird species in the size, structure and distribution of taste buds seem to be associated with diet type and other ecological adaptations. Birds also seem to have a smaller repertoire of bitter taste receptors (T2Rs) and lack some taste receptors such as the T1R2 involved in sweet taste perception. This has opened new areas of research focusing on taste perception mechanisms independent of GPCR taste receptors and the discovery of evolutionary shifts in the molecular function of taste receptors adapting to ecological niches in birds. For example, recent discoveries have shown that the amino acid taste receptor dimer T1R1-T1R3 have mutated to sense simple sugars in almost half of the living bird species, or SGLT1 has been proposed as a part of a T1R2-independent sweet taste sensing in chicken. The aim of this review is to present the scientific data known to date related to the avian taste system across species and its impact on dietary choices including domestic and wild species.

Identification and prediction of milk-derived bitter taste peptides based on peptidomics technology and machine learning method

Bitter taste peptides (BPs) are vital for drug and nutrition research, but large-scale screening of them is still time-consuming and costly. This study developed a complete workflow for screening BPs based on peptidomics technology and machine learning method. Using an expanded dataset and a new combination of BPs’ characteristic factors, a novel classification prediction model (CPM-BP) based on the Light Gradient Boosting Machine algorithm was constructed with an accuracy of 90.3 % for predicting BPs. Among 724 significantly different peptides between spoiled and fresh UHT milk, 180 potential BPs were predicted using CPM-BP and eleven of them were previously reported. One known BP (FALPQYLK) and three predicted potential BPs (FALPQYL, FFVAPFPEVFGKE, EMPFPKYP) were verified by determination of calcium mobilization of HEK293T cells expressing human bitter taste receptor T2R4 (hT2R4). Three potential BPs could activate the hT2R4 and are demonstrated to be BPs, which proved the effectiveness of CPM-BP.

Bitter taste receptors along the gastrointestinal tract: comparison between humans and rodents.

For decades bitter taste receptors (TAS2R) were thought to be located only in the mouth and to serve as sensors for nutrients and harmful substances. However, in recent years Tas2r have also been reported in extraoral tissues such as the skin, the lungs, and the intestine, where their function is still uncertain. To better understand the physiological role of these receptors, in this paper we focused on the intestine, an organ in which their activation may be similar to the receptors found in the mouth. We compare the relative presence of these receptors along the gastrointestinal tract in three main species of biomedical research (mice, rats and humans) using sequence homology. Current data from studies of rodents are scarce and while more data are available in humans, they are still deficient. Our results indicate, unexpectedly, that the reported expression profiles do not always coincide between species even if the receptors are orthologs. This may be due not only to evolutionary divergence of the species but also to their adaptation to different dietary patterns. Further studies are needed in order to develop an integrated vision of these receptors and their physiological functionality along the gastrointestinal tract.

Enhancement of debitterness, water-solubility, and neuroprotective effects of naringin by transglucosylation.

Naringin found in citrus fruits is a flavanone glycoside with numerous biological activities. However, the bitterness, low water-solubility, and low bioavailability of naringin are the main issues limiting its use in the pharmaceutical and nutraceutical industries. Herein, a glucansucrase from isolated Leuconostoc citreum NY87 was used for trans-α-glucosylattion of naringin by using sucrose as substrate. Two naringin glucosides (O-α-D-glucosyl-(1'''' → 6″) naringin (compound 1) and 4'-O-α-D-glucosyl naringin (compound 2)) were purified and determined their structures by nuclear magnetic resonance. The optimization condition for the synthesis of compound 1 was obtained at 10mM naringin, 200mM sucrose, and 337.5mU/mL at 28°C for 24h by response surface methodology method. Compound 1 and compound 2 showed 1896- and 3272 times higher water solubility than naringin. Furthermore, the bitterness via the human bitter taste receptor TAS2R39 displayed that compound 1 was reduced 2.9 times bitterness compared with naringin, while compound 2 did not express bitterness at 1mM. Both compounds expressed higher neuroprotective effects than naringin on human neuroblastoma SH-SY5Y cells treated with 5mM scopolamine based on cell viability and cortisol content. Compound 1 reduced acetylcholinesterase activity more than naringin and compound 2. These results indicate that naringin glucosides could be utilized as functional material in the nutraceutical and pharmaceutical industries. KEY POINTS: • A novel O-α-D-glucosyl-(1 → 6) naringin was synthesized using glucansucrase from L. citreum NY87. • Naringin glucosides improved water-solubility and neuroprotective effects on SH-SY5Y cells. • Naringin glucosides showed a decrease in bitterness on bitter taste receptor 39.

Nebulized caffeine alleviates airway hyperresponsiveness in a murine asthma model.

The clinical definition of "difficult asthma" has expanded recently to include an ever-growing subset of patients with symptoms that cannot be controlled by conventional means, forcing the medical community to develop innovative therapeutics. Beneficial effects of coffee for subjects with asthma, primarily the effect of methylxanthine components, have long been described. Methylxanthines, including theophylline and caffeine, inhibit phosphodiesterases and downstream cAMP signaling to prevent mast cell degranulation while promoting immunomodulation (Peleman RA, Kips JC, Pauwels RA. Clin Exp Allergy 28: 53-56, 1998; Deshpande DA, Wang WCH, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JSK, Liggett SB. Nat Med 16: 1299-1304, 2010). Caffeine is also a bitter taste receptor agonist, binding to taste-sensing type 2 receptors (TAS2R) before releasing calcium to hyperpolarize airway smooth muscle membranes, inducing bronchodilation (Workman AD, Palmer JN, Adappa ND, Cohen NA. Curr Allergy Asthma Rep 15: 72, 2015; Devillier P, Naline E, Grassin-Delyle S. Pharmacol Ther 155: 11-21, 2015). Theophylline is conventionally used to treat asthma, whereas, according to the literature, the dosage required for orally administered caffeine has yielded modest improvement (Alfaro TM, Monteiro RA, Cunha RA, Cordeiro CR. Clin Respir J 12: 1283-1294, 2018). We sought to determine whether aerosolization of ultrafine caffeine particles (2.5-4 μm) directly to the lungs of susceptible A/J mice challenged with methacholine would improve pulmonary function via forced oscillation technique. In addition, we assessed whether nebulization of caffeine leads to changes in lung pathophysiology and bronchoalveolar lavage cell profiles. We found that mice that received aerosolized caffeine had statistically significant decreases in maximum airway resistance [6.3 vs. 3.9 cmH2O·s/mL at 62.5 mg/mL caffeine; confidence interval (CI) = -4.3, -0.4; P = 0.02] and significant delays in the time required to reach maximum resistance compared with that of controls (64.7 vs. 172.1 sec at 62.5 mg/mL caffeine, CI = 96.0, 118.9; P < 0.0001). Nebulized caffeine yielded a consistent effect on airway hyperresponsiveness at a range of doses without evidence of significant pathology relative to vehicle control.NEW & NOTEWORTHY For decades, coffee has been shown to improve symptoms in patients with asthma. One component, theophylline, is conventionally used to treat asthma, whereas the dosage required for orally administered caffeine has yielded modest improvement. We sought to determine whether aerosolization of caffeine directly to the lungs of susceptible A/J mice challenged with methacholine would alter pulmonary function via forced oscillation technique. We found nebulized caffeine yielded a consistent improvement on murine AHR.

Structural and functional studies on bitter taste receptors

Structural and functional studies on bitter taste receptors

The bitter taste receptor (TAS2R) agonist denatonium promotes a strong relaxation of rat corpus cavernosum

Bitter taste receptors (TAS2R) are found in numerous extra-oral tissues, including smooth muscle (SM) cells in both vascular and visceral tissues. Upon activation, TAS2R stimulate the relaxation of the SM. Nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway is involved in penile erection, and type 5 phosphodiesterase (PDE5) inhibitors, a cGMP-specific hydrolase are used as first-line treatments for erectile dysfunction (ED). Nevertheless, PDE5 inhibitors are ineffective in a considerable number of patients, prompting research into alternative pharmacological targets for ED. Since TAS2R agonists regulate SM contractility, this study investigates the role of TAS2Rs in rat corpus cavernosum (CC). We performed immunohistochemistry to detect TAS2R10, isometric force recordings for TAS2R agonists denatonium and chloroquine, the slow-release H2S donor GYY 4137, the NO donor SNAP, the β-adrenoceptor agonist isoproterenol and electrical field stimulation (EFS), as well as measurement of endogenous hydrogen sulfide (H2S) production. The immunofluorescence staining indicated that TAS2R10 was broadly expressed in the CC SM and to some extent in the nerve fibers. Denatonium, chloroquine, SNAP, and isoproterenol cause potent dose-dependent SM relaxations. H2S production was decreased by NO and H2S synthase inhibitors, while it was enhanced by denatonium. In addition, denatonium increased the relaxations induced by GYY 4137 and SNAP but failed to modify EFS- and isoproterenol-induced responses. These results suggest neuronal and SM TAS2R10 expression in the rat CC, where denatonium induces a strong SM relaxation per se and promotes the H2S- and NO-mediated inhibitory gaseous neurotransmission. Thus, TAS2R10 might represent a valuable therapeutic target in ED.

Bitter Is Better: Wild Greens Used in the Blue Zone of Ikaria, Greece.

The current study reports an ethnobotanical field investigation of traditionally gathered and consumed wild greens (Chorta) in one of the five so-called Blue Zones in the world: Ikaria Isle, Greece. Through 31 semi-structured interviews, a total of 56 wild green plants were documented along with their culinary uses, linguistic labels, and locally perceived tastes. Most of the gathered greens were described as bitter and associated with members of Asteraceae and Brassicaceae botanical families (31%), while among the top-quoted wild greens, species belonging to these two plant families accounted for 50% of the wild vegetables, which were consumed mostly cooked. Cross-cultural comparison with foraging in other areas of the central-eastern Mediterranean and the Near East demonstrated a remarkable overlapping of Ikarian greens with Cretan and Sicilian, as well as in the prevalence of bitter-tasting botanical genera. Important differences with other wild greens-related food heritage were found, most notably with the Armenian and Kurdish ones, which do not commonly feature many bitter greens. The proven role of extra-oral bitter taste receptors in the modulation of gastric emptying, glucose absorption and crosstalk with microbiota opens new ways of looking at these differences, in particular with regard to possible health implications. The present study is also an important attempt to preserve and document the bio-cultural gastronomic heritage of Chorta as a quintessential part of the Mediterranean diet. The study recommends that nutritionists, food scientists, and historians, as well as policymakers and practitioners, pay the required attention to traditional rural dietary systems as models of sustainable health.

Hop bitterness in beer evaluated by computational analysis

Beer flavour and aroma are greatly influenced by the hop(s) employed in the brewing process. The iso-α-acids post wort boiling are the major compounds responsible for bitterness, which are detected by the bitter taste receptors (TAS2Rs) in oral taste buds. This family of receptors is activated in the presence of bitter molecules, which send chemical signals to the brain, making it possible to differentiate whether the detected molecules have a pleasant taste (or not). It is of interest to predict the behaviour of hop compounds towards bitter receptors such that the bitterness of different hop varieties can be predicted based on quantitative analysis of composition. Computational simulation, based in high-performance computing (HPC), allow the simulation of interactions of molecules with the various TAS2Rs, enabling the prediction the bitterness of these hop compounds. These techniques, will soon enable the design of beverages with customised flavours, greatly reducing the need for experimental evaluation. In this work, α and β-acids, iso-α-acids, and prenylflavonoids are analysed against the bitter receptors TAS2R10, TAS2R14 and TAS2R46. Using computational blind docking and molecular dynamics, xanthohumol was identified to have the highest bitter profile.

Physiological activation of human and mouse bitter taste receptors by bile acids

Beside the oral cavity, bitter taste receptors are expressed in several non-gustatory tissues. Whether extra-oral bitter taste receptors function as sensors for endogenous agonists is unknown. To address this question, we devised functional experiments combined with molecular modeling approaches to investigate human and mouse receptors using a variety of bile acids as candidate agonists. We show that five human and six mouse receptors are responsive to an array of bile acids. Moreover, their activation threshold concentrations match published data of bile acid concentrations in human body fluids, suggesting a putative physiological activation of non-gustatory bitter receptors. We conclude that these receptors could serve as sensors for endogenous bile acid levels. These results also indicate that bitter receptor evolution may not be driven solely by foodstuff or xenobiotic stimuli, but also depend on endogenous ligands. The determined bitter receptor activation profiles of bile acids now enable detailed physiological model studies.

VARIATIONS IN THE PERCEPTION OF BITTER TASTE MAY MODULATE THE RISK OF HYPERTENSION

Objective: The perception of bitter taste conditioned by the TAS2R38 gene (combined Proline/Alanine/Valine and Isoleucine phenotypes) may be associated with food consumption. Individuals with one copy of PAV are bitter tasters, with two copies of AVI are non-bitter tasters, and with AAV &lt; AAI &lt; PAI are intermediate bitter tasters. Consumption salt balance is determined by the function of the epithelial sodium channels that lead to its preference and the bitter taste receptors associated with its aversion. In turn, a chronic high salt intake was associated with the inhibition of bitter receptors with less salty taste aversion leading to potential higher consumption and risk of hypertension. The objective was to evaluate the influence of bitter taste perception on the risk of arterial hypertension. Design and method: DNA from 339 individuals was quantified and genotyped by reverse transcription followed by polymerase chain reaction (RT-PCR). Blood pressure was determined by standard methods. Arterial hypertension was diagnosed in 141 individuals who were compared with 198 normotensive individuals. Thyroid functional status is determined by clinical history, physical examination, FT4, FT3, TSH, antiperoxidase, antithyroglobulin, and TRAB antibodies. Hypothyroidism at 33.3%, hyperthyroidism 14.3% and euthyroidism 52.35%. Statistics: chi2 and t-Student, considering significance &lt;0.05. Results: The frequencies of the TAS2R38 diplotypes were: PVI/PVI (26%); PVV/PVI (0.9%); PVV/AVI(10.6%); PVV/AVV(0.9%); AVV/AVV(2.4%); PAI/PVI(0.3%); PAV/PVI(5.95%); PAV/AVI(37.5%); AAV/AAV(12.7%); PAV/AAV(2.75%) and PAV/AAI(0.3%). The TAS2R38 AAV/AAV and PAV/AAV diplotypes showed a lower risk of hypertension adjusted for thyroid dysfunction, compared to the remaining diplotypes of this gene, with OR = 0.458[0.236-0.887], p = 0.021. Other diplotypes showed no significant association. Conclusions: Individuals with bitter tasting associated with AAV genotypes may be less likely to develop hypertension compared to other bitter tasters. The lower risk of hypertension in these genotypes may be associated with greater functionality of bitter taste receptors associated with aversion to salt intake. In conclusion, the genetic polymorphisms of the bitter taste gene may influence the risk for arterial hypertension and may therefore be considered potential future therapeutic targets. The absence of bitter-insensitive individuals (AVI/AVI) in this sample limits the understanding of the influence of these genotypes on the risk of hypertension.

Association between Genetic Variation in the TAS2R38 Bitter Taste Receptor and Propylthiouracil Bitter Taste Thresholds among Adults Living in Japan Using the Modified 2AFC Procedure with the Quest Method.

Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual's taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene, TAS2R38, with the bitter compound 6-n-propylthiouracil (PROP). We precisely detected the threshold of PROP bitter perception by conducting the modified two-alternative forced-choice (2AFC) procedure with the Bayesian staircase procedure of the QUEST method and examined genetic variation in TAS2R38 in a Japanese population. There were significant differences in PROP threshold between the three TAS2R38 genotype pairs for 79 subjects: PAV/PAV vs AVI/AVI, p < 0.001; PAV/AVI vs AVI/AVI, p < 0.001; and PAV/PAV vs PAV/AVI, p < 0.01. Our results quantified individual bitter perception as QUEST threshold values: the PROP bitter perception of individuals with the PAV/PAV or PAV/AVI genotypes was tens to fifty times more sensitive than that of an individual with the AVI/AVI genotype. Our analyses provide a basic model for the accurate estimation of taste thresholds using the modified 2AFC with the QUEST approach.

Interkingdom Detection of Bacterial Quorum-Sensing Molecules by Mammalian Taste Receptors.

Bitter and sweet taste G protein-coupled receptors (known as T2Rs and T1Rs, respectively) were originally identified in type II taste cells on the tongue, where they signal perception of bitter and sweet tastes, respectively. Over the past ~15 years, taste receptors have been identified in cells all over the body, demonstrating a more general chemosensory role beyond taste. Bitter and sweet taste receptors regulate gut epithelial function, pancreatic β cell secretion, thyroid hormone secretion, adipocyte function, and many other processes. Emerging data from a variety of tissues suggest that taste receptors are also used by mammalian cells to "eavesdrop" on bacterial communications. These receptors are activated by several quorum-sensing molecules, including acyl-homoserine lactones and quinolones from Gram-negative bacteria such as Pseudomonas aeruginosa, competence stimulating peptides from Streptococcus mutans, and D-amino acids from Staphylococcus aureus. Taste receptors are an arm of immune surveillance similar to Toll-like receptors and other pattern recognition receptors. Because they are activated by quorum-sensing molecules, taste receptors report information about microbial population density based on the chemical composition of the extracellular environment. This review summarizes current knowledge of bacterial activation of taste receptors and identifies important questions remaining in this field.

Taste 2 receptors in GtoPdb v.2023.1

Taste 2 receptors or Bitter taste receptors (TAS2Rs) are G protein-coupled receptors expressed in oral sensory cells and a variety of non-gustatory tissues. The ~25 human TAS2Rs share low amino acid sequence identities with other GPCR families and are classified as broadly tuned "generalist" receptors with numerous, chemically diverse bitter agonists, as narrowly tuned "specialist" receptors with very few activators, as intermediately tuned receptors with an average number of agonists, or receptors specialized to interact with chemically defined activators [32]. The number of functional bitter taste receptor genes varies among species and orthologues might not be functionally conserved. Due to their expression in various tissues, the signal transduction of TAS2Rs is complex. Some TAS2Rs interact with drugs such as analgesic, anti-inflammatory, and antibacterial compounds. The specialist database BitterDB contains additional information on bitter compounds and receptors [14].

Activation Profile of TAS2R2, the 26th Human Bitter Taste Receptor.

To avoid ingestion of potentially harmful substances, humans are equipped with about 25 bitter taste receptor genes (TAS2R) expressed in oral taste cells. Humans exhibit considerable variance in their bitter tasting abilities, which are associated with genetic polymorphisms in bitter taste receptor genes. One of these variant receptor genes, TAS2R2, is initially believed to represent a pseudogene. However, TAS2R2 exists in a putative functional variant within some populations and can therefore be considered as an additional functional bitter taste receptor. To learn more about the function of the experimentally neglected TAS2R2, a functional screening with 122 bitter compounds is performed. The study observes responses with eight of the 122 bitter substances and identifies the substance phenylbutazone as a unique activator of TAS2R2 among the family of TAS2Rs, thus filling one more gap in the array of cognate bitter substances. The comprehensive characterization of the receptive range of TAS2R2 allows the classification into the group of TAS2Rs with a medium number of bitter agonists. The variability of bitter taste and its potential influences on food choice in some human populations may be even higher than assumed.

Non-Volatile Compounds Involved in Bitterness and Astringency of Pulses: A Review.

Despite the many advantages of pulses, they are characterised by off-flavours that limit their consumption. Off-notes, bitterness and astringency contribute to negative perceptions of pulses. Several hypotheses have assumed that non-volatile compounds, including saponins, phenolic compounds, and alkaloids, are responsible for pulse bitterness and astringency. This review aims to provide an overview highlighting the non-volatile compounds identified in pulses and their bitter and/or astringent characteristics to suggest their potential involvement in pulse off-flavours. Sensorial analyses are mainly used to describe the bitterness and astringency of molecules. However, in vitro cellular assays have shown the activation of bitter taste receptors by many phenolic compounds, suggesting their potential involvement in pulse bitterness. A better knowledge of the non-volatile compounds involved in the off-flavours should enable the creation of efficient strategies to limit their impact on overall perception and increase consumer acceptability.

Taste coding of heavy metal ion-induced avoidance in Drosophila

Increasing pollution of heavy metals poses great risks to animals globally. Their survival likely relies on an ability to detect and avoid harmful heavy metal ions (HMIs). Currently, little is known about the neural mechanisms of HMI detection. Here, we show that Drosophila and related species of Drosophilidae actively avoid toxic HMIs at micromolar concentrations. The high sensitivity to HMIs is biologically relevant. Particularly, their sensitivity to cadmium is as high as that to the most bitter substance, denatonium. Detection of HMIs in food requires Gr66a + gustatory neurons but is independent of bitter-taste receptors. In these neurons, the ionotropic receptors IR76b, IR25a, and IR7a are required for the perception of heavy metals. Furthermore, IR47a mediates the activation of a distinct group of non-Gr66a + gustatory neurons elicited by HMIs. Together, our findings reveal a surprising taste quality represented by noxious metal ions.