Activation Of Taste Receptors Research Articles

Bitter taste receptor activation by cholesterol and an intracellular tastant.

Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors1. Among the 26 members of the TAS2Rs, TAS2R14 is highly expressed in extraoral tissues and mediates the responses to more than 100 structurally diverse tastants2-6, although the molecular mechanisms for recognizing diverse chemicals and initiating cellular signalling are still poorly understood. Here we report two cryo-electron microscopy structures for TAS2R14 complexed with Ggust (also known as gustducin) and Gi1. Both structures have an orthosteric binding pocket occupied by endogenous cholesterol as well as an intracellular allosteric site bound by the bitter tastant cmpd28.1, including a direct interaction with the α5 helix of Ggust and Gi1. Computational and biochemical studies validate both ligand interactions. Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.

Sensory and molecular insights into the bitterness of Wuyi rock tea

Wuyi Rock Tea (WRT) is widely appreciated for its unique rocky flavor and floral essence. However, the characterization of taste attributes, particularly bitterness, in this premium tea remains largely underexplored. This study aims to assess the perception of bitterness in WRT through an integrated approach, including sensory evaluation, phenolic compound analysis, and cell-based calcium imaging assay. Sensory evaluation revealed distinct bitterness intensities among nine selected typical WRT samples. Utilizing UHPLC-Q-Orbitrap-MS, 54 phenolics were tentatively identified, comprising of 24 flavanols, 18 flavonols, and 12 phenolic acids. The cell-based calcium imaging assay revealed diverse intracellular calcium responses and half-maximum effective concentration (EC50) values across the tested samples. Notably, correlation analysis unveiled a strong negative correlation between sensory scores and EC50 values. Furthermore, 11 individual phenolic compounds, such as epigallocatechin gallate and epicatechin gallate, demonstrated significant correlation with sensory scores and bitter taste receptor activation, suggesting their potential role as key contributors shaping the bitter taste perception of WRT. This study provides comprehensive insights into the nuanced bitterness of WRT, bridging sensory and molecular perspectives to enhance our understanding of the taste profile of this premium tea.

Identification of mozambioside roasting products and their bitter taste receptor activation

Arabica coffee contains the bitter-tasting diterpene glycoside mozambioside, which degrades during coffee roasting, leading to yet unknown structurally related degradation products with possibly similar bitter-receptor-activating properties.The study aimed at the generation, isolation, and structure elucidation of individual pyrolysis products of mozambioside and characterization of bitter receptor activation by in vitro analysis in HEK 293T-Gα16gust44 cells.The new compounds 17-O-β-d-glucosyl-11-hydroxycafestol-2-on, 11-O-β-d-glucosyl-16-desoxycafestol-2-on, 11-O-β-d-glucosyl-(S)-16-desoxy-17-oxocafestol-2-on, 11-O-β-d-glucosyl-15,16-dehydrocafestol-2-on, and 11-O-β-d-glucosyl-(R)-16-desoxy-17-oxocafestol-2-on were isolated from pyrolyzed mozambioside by HPLC and identified by NMR and UHPLC-ToF-MS. Roasting products 11-O-β-d-glucosyl-(S)-16-desoxy-17-oxocafestol-2-on, 11-O-β-d-glucosyl-15,16-dehydrocafestol-2-on, and 11-O-β-d-glucosyl-(R)-16-desoxy-17-oxocafestol-2-on had lower bitter receptor activation thresholds compared to mozambioside.Molecular docking simulations revealed the binding modes of the compounds 11-O-β-d-glucosyl-15,16-dehydrocafestol-2-on and 11-O-β-d-glucosyl-(R)-16-desoxy-17-oxocafestol-2-on and their aglycone 11-hydroxycafestol-2-on in the two cognate receptors TAS2R43 and TAS2R46.The newly discovered roasting products 17-O-β-d-glucosyl-11-hydroxycafestol-2-on, 11-O-β-d-glucosyl-(S)-16-desoxy-17-oxocafestol-2-on, 11-O-β-d-glucosyl-15,16-dehydrocafestol-2-on, and 11-O-β-d-glucosyl-(R)-16-desoxy-17-oxocafestol-2-on were detected in authentic roast coffee brew by UHPLC-ToF-MS and could contribute to coffee's bitter taste impression.

Activation of bitter taste receptors by saponins and alkaloids identified in faba beans (Vicia faba L. minor).

Despite their interests, faba beans are characterised by bitterness but little is known about its compounds that activate the 25 human bitter receptors (TAS2Rs). This study aimed to determine the bitter molecules in faba beans, especially saponins and alkaloids. These molecules were quantified by UHPLC-HRMS in flour, starch and protein fractions of 3 faba bean cultivars. The fractions from the low-alkaloid cultivar and the protein fractions exhibited higher saponin content. Vicine and convicine were highly correlated with bitter perception. The bitterness of soyasaponin βb and alkaloids was studied using a cellular approach. Soyasaponin βb activated 11 TAS2Rs, including TAS2R42 whereas vicine activated only TAS2R16. The high vicine content should explain the faba bean bitterness considering that concentration of soyasaponin βb was low. This research provides a better understanding of the bitter molecules in faba beans. Selection of low-alkaloid ingredients or alkaloid removal treatments could improve the faba bean flavour.

Impact of feeding diets with enhanced vegetable protein content and presence of umami taste-stimulating additive on gastrointestinal amino acid sensing and feed intake regulation in rainbow trout

The regulation of feed intake in fish is dependent upon different neuroendocrine and metabolic mechanisms including amino acid sensing in the gastrointestinal tract (GIT). However, there is little information regarding the impact of diets on such mechanisms. Therefore, in this study, we fed rainbow trout (Oncorhynchus mykiss) with 3 diets: a diet with high content of fishmeal and low content of soybean protein concentrate (SPC) (HF), a diet with a reduced content of fishmeal and high content of SPC (LF), and the LF diet supplemented with an umami taste-stimulating additive (LFU). Fish were fed ad libitum once a day for 4 weeks, with no significant differences being registered in feed intake among groups. At the end of the feeding trial, we collected samples of different areas of the GIT (stomach, proximal and distal intestine) and hypothalamus at different times: after 48 h of fasting (time 0), and 1 h, 4 h, and 24 h after feeding. We evaluated the activity of pepsin in the stomach and trypsin and chymotrypsin in the proximal intestine, as well as mRNA abundance of transcripts encoding amino acid transporters and taste receptors, intracellular signalling molecules, and hormones. Moreover, we assessed the hypothalamic mRNA abundance of neuropeptides involved in feed intake regulation. Feeding rainbow trout with LF did not result in marked alterations in parameters related to digestive function and amino acid sensing in the rainbow trout GIT, nor in the expression of gastrointestinal hormones (except cck) and hypothalamic neuropeptides. In contrast, supplementation of the LF diet with an umami taste-stimulating additive resulted in a general improvement of digestive or absorptive function (increased protein, dry matter and energy digestibility, and earlier peak in plasma amino acid levels) and activation of gut-brain axis mechanisms involved in feed intake regulation through the transcriptional activation of amino acid transporters, taste receptors, signalling molecules, and hormones. These results demonstrate that the dietary inclusion of umami receptor stimulants has the potential to improve fish physiological responses to the rise in levels of vegetable protein in the diet.

Morus alba L. Leaves (WML) Modulate Sweet (TAS1R) and Bitter (TAS2R) Taste in the Studies on Human Receptors – A New Perspective on the Utilization of White Mulberry Leaves in Food Production?

From the nutritional perspective, the main direction of the utilization of white mulberry (Morus alba L.) parts so far has been to produce dietary supplements or functional foods for individuals with diabetes or over-weight. Its leaves are widely known as a valuable source of bioactive compounds responsible for its antioxidant and antidiabetic effects, both in animals and humans. The authors found that processed leaves can also be investigated as potential bitter and/or sweet taste modulators—an important property of new functional foods. The study aimed to validate the inhibitory effect of Morus alba L. on the TAS2R3 and TAS2R13 bitter taste and TSA1R2/TSA1R3 receptors and determine the changes that the conditioning process caused in such receptors. The effect on the receptors was evaluated in specially transfected HEK293T cells, and the inhibition ratio was measured using the calcium release test. Moreover, the stability of phenolics in the simulated intestinal in vitro digestion process was determined. Results showed that the Morus alba leaf extracts were rich in gallic, chlorogenic and caffeic acids together with rutin and quercetin 3-(6-malonyl)-glucoside, while the conditioning process positively affected their amount. Most identified phenolics were reduced during in vitro digestion. In the taste receptors test, it was found that the phytochemicals from conditioned Morus alba leaf extract enhanced sweet taste, together with a reduction of bitter taste receptor activity in some cases. To conclude, the study has found that Morus alba, especially when conditioned for 4 h, seems to be a valuable modulator of taste, which should be considered in future research as a crucial reason for its new utilization.

Limited introgression from non-native commercial strains and signatures of adaptation in the key pollinator Bombus terrestris.

Insect pollination is fundamental for natural ecosystems and agricultural crops. The bumblebee species Bombus terrestris has become a popular choice for commercial crop pollination worldwide due to its effectiveness and ease of mass rearing. Bumblebee colonies are mass produced for the pollination of more than 20 crops and imported into over 50 countries including countries outside their native ranges, and the risk of invasion by commercial non-native bumblebees is considered an emerging issue for global conservation and biological diversity. Here, we use genome-wide data from seven wild populations close to and far from farms using commercial colonies, as well as commercial populations, to investigate the implications of utilizing commercial bumblebee subspecies in the UK. We find evidence for generally low levels of introgression between commercial and wild bees, with higher admixture proportions in the bees occurring close to farms. We identify genomic regions putatively involved in local and global adaptation, and genes in locally adaptive regions were found to be enriched for functions related to taste receptor activity, oxidoreductase activity, fatty acid and lipid biosynthetic processes. Despite more than 30 years of bumblebee colony importation into the UK, we observe low impact on the genetic integrity of local B. terrestris populations, but we highlight that even limited introgression might negatively affect locally adapted populations.

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.

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.

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.

A comprehensive review of the metabolism of citrus flavonoids and their binding to bitter taste receptors.

Citrus is an important source of flavonoids in our daily diet. Citrus flavonoids have antioxidant, anticancer, anti-inflammatory, and cardiovascular disease prevention functions. Studies have shown that some pharmaceutical values of flavonoids may be related to their binding to bitter taste receptors, thus activating downstream signal transduction pathways; however, the underlying mechanism has not been systematically elucidated. In this paper, the biosynthesis pathway and the absorption and metabolism of citrus flavonoids were briefly reviewed, and the relationship between flavonoid structure and bitter taste intensity was investigated. In addition, the pharmacological effects of bitter flavonoids and the activation of bitter taste receptors in combating various diseases were discussed. This review provides an important basis for the targeted design of citrus flavonoid structures to make them more biologically active and more attractive as powerful drugs for the effective treatment of chronic diseases such as obesity, asthma, and neurological diseases.

Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.

Lopinavir and ritonavir (LPV/r) are the primary anti-human immunodeficiency virus (HIV) drugs recommended by the World Health Organization for treating children aged 3 years and above who are infected with the HIV. These drugs are typically available in liquid formulations to aid in dosing for children who cannot swallow tablets. However, the strong bitter taste associated with these medications can be a significant obstacle to adherence, particularly in young children, and can jeopardize the effectiveness of the treatment. Studies have shown that poor palatability can affect the survival rate of HIV-infected children. Therefore, developing more child-friendly protease inhibitor formulations, particularly those with improved taste, is critical for children with HIV. The molecular mechanism by which lopinavir and ritonavir activate bitter taste receptors, TAS2Rs, is not yet clear. In this study, we utilized a calcium mobilization assay to characterize the activation of bitter taste receptors by lopinavir and ritonavir. We discovered that lopinavir activates TAS2R1 and TAS2R13, while ritonavir activates TAS2R1, TAS2R8, TAS2R13, and TAS2R14. The development of bitter taste blockers that target these receptors with a safe profile would be highly desirable in eliminating the unpleasant bitter taste of these anti-HIV drugs.

An overview of bitter compounds in foodstuffs: Classifications, evaluation methods for sensory contribution, separation and identification techniques, and mechanism of bitter taste transduction.

The bitter taste is generally considered an undesirable sensory attribute. However, bitter-tasting compounds can significantly affect the overall flavor of many foods and beverages and endow them with various beneficial effects on human health. To better understand the relationship between chemical structure and bitterness, this paper has summarized the bitter compounds in foodstuffs and classified them based on the basic skeletons. Only those bitter compounds that are confirmed by human sensory evaluation have been included in this paper. To develop food products that satisfy consumer preferences, correctly ranking the key bitter compounds in foodstuffs according to their contributions to the overall bitterness intensity is the precondition. Generally, three methods were applied to screen out the key bitter compounds in foods and beverages and evaluate their sensory contributions, including dose-over-threshold factors, taste dilution analysis, and spectrum descriptive analysis method. This paper has discussed in detail the mechanisms and applications of these three methods. Typical procedures for separating and identifying the main bitter compounds in foodstuffs have also been summarized. Additionally, the activation of human bitter taste receptors (TAS2Rs) and the mechanisms of bitter taste transduction are outlined. Ultimately, a conclusion has been drawn to highlight the current problems and propose potential directions for further research.

Synergistic Effect of Kokumi-Active γ-Glutamyl Peptides and l-Glutamate on Enhancing Umami Sensation and Stimulating Cholecystokinin Secretion via T1R1/T1R3 Activation in STC-1 Cells.

This study aimed to investigate the synergistic effect of γ-glutamyl peptides (γEL, γEV, and γEγEV) and l-glutamate (MSG) on the activation of the umami receptor (T1R1/T1R3) in relation to enhanced umami taste and promoted cholecystokinin (CCK) secretion. The synergy of γ-glutamyl peptides and MSG (1-15 mM, 1:1) caused a significant increase in both the umami taste score by 0.218 ± 0.015-1.216 ± 0.031 times and the CCK secretion by 41.41 ± 6.46-201.16 ± 12.91% when compared to the group treated with individual MSG. The increase in CCK secretion promoted by γ-glutamyl peptides was only reduced by 11.54 ± 0.01-45.65 ± 3.58% after adding yjr CaSR inhibitor (NPS 2143), implying that there were other receptors besides CaSR involved in the stimulation of CCK secretion. The mixture of γEγEV and MSG synergistically increased the intracellular calcium release by 111.26 ± 11.94-135.28 ± 16.60% in STC-1 and 108.47 ± 7.89-152.33 ± 26.26% in HEK 293 compared to MSG. The protein expression for T1R1/T1R3 was increased, indicating that the mixture can activate T1R1/T1R3. The amino acids V277, S147, and D190 of T1R3 can be critical for the binding of γEγEV to T1R3. This is the first report on the synergistic effect of taste-active substances on taste sensation and hormone release via taste receptor activation.

Bitter Peptides YFYPEL, VAPFPEVF, and YQEPVLGPVRGPFPIIV, Released during Gastric Digestion of Casein, Stimulate Mechanisms of Gastric Acid Secretion via Bitter Taste Receptors TAS2R16 and TAS2R38.

Eating satiating, protein-rich foods is one of the key aspects of modern diet, although a bitter off-taste often limits the application of some proteins and protein hydrolysates, especially in processed foods. Previous studies of our group demonstrated that bitter-tasting food constituents, such as caffeine, stimulate mechanisms of gastric acid secretion as a signal of gastric satiation and a key process of gastric protein digestion via activation of bitter taste receptors (TAS2Rs). Here, we tried to elucidate whether dietary non-bitter-tasting casein is intra-gastrically degraded into bitter peptides that stimulate mechanisms of gastric acid secretion in physiologically achievable concentrations. An in vitro model of gastric digestion was verified by casein-fed pigs, and the peptides resulting from gastric digestion were identified by liquid chromatography–time-of-flight-mass spectrometry. The bitterness of five selected casein-derived peptides was validated by sensory analyses and by an in vitro screening approach based on human gastric parietal cells (HGT-1). For three of these peptides (YFYPEL, VAPFPEVF, and YQEPVLGPVRGPFPIIV), an upregulation of gene expression of TAS2R16 and TAS2R38 was observed. The functional involvement of these TAS2Rs was verified by siRNA knock-down (kd) experiments in HGT-1 cells. This resulted in a reduction of the mean proton secretion promoted by the peptides by up to 86.3 ± 9.9% for TAS2R16kd (p < 0.0001) cells and by up to 62.8 ± 7.0% for TAS2R38kd (p < 0.0001) cells compared with mock-transfected cells.

New strategies for identifying and masking the bitter taste in traditional herbal medicines: The example of Huanglian Jiedu Decoction.

Suppressing the bitter taste of traditional Chinese medicine (TCM) largely has been a major clinical challenge due to complex and diverse metabolites and high dispersion of bitter metabolites in liquid preparations. In this work, we developed a novel strategy for recognizing bitter substances, hiding their bitter taste, and elucidated the mechanism of flavor masking in TCM. Huanglian Jie-Du Decoction (HLJDD) with an intense bitter taste was studied as a typical case. UHPLC-MS/MS was used to analyze the chemical components in HLJDD, whereas the bitter substances were identified by pharmacophores. Additionally, the screening results of the pharmacophores were further validated by using experimental assays. The mask formula of HLJDD was effectively screened under the condition of clear bitter substances. Subsequently, computational chemistry, molecular docking, and infrared characterization (IR) techniques were then used to explicate the mechanism of flavor masking. Consequently, neotame, γ-CD, and mPEG2000-PLLA2000 significantly reduced the bitterness of HLJDD. Specifically, mPEG2000-PLLA2000 increased the colloid proportion in the decoction system and minimized the distribution of bitter components in the real solution. Sweetener neotame suppressed the perception of bitter taste and inhibited bitter taste receptor activation to eventually reduce the bitter taste. The γ-CD included in the decoction bound the hydrophobic groups of the bitter metabolites in real solution and “packed” all or part of the bitter metabolites into the “cavity”. We established a novel approach for screening bitter substances in TCM by integrating virtual screening and experimental assays. Based on this strategy, the bitter taste masking of TCM was performed from three different aspects, namely, changing the drug phase state, component distribution, and interfering with bitter taste signal transduction. Collectively, the methods achieved a significant effect on bitter taste suppression and taste masking. Our findings will provide a novel strategy for masking the taste of TCM liquid preparation/decoction, which will in return help in improving the clinical efficacy of TCM.

Taste Receptor Activation in Tracheal Brush Cells by Denatonium Modulates ENaC Channels via Ca2+, cAMP and ACh.

Mucociliary clearance is a primary defence mechanism of the airways consisting of two components, ciliary beating and transepithelial ion transport (ISC). Specialised chemosensory cholinergic epithelial cells, named brush cells (BC), are involved in regulating various physiological and immunological processes. However, it remains unclear if BC influence ISC. In murine tracheae, denatonium, a taste receptor agonist, reduced basal ISC in a concentration-dependent manner (EC50 397 µM). The inhibition of bitter taste signalling components with gallein (Gβγ subunits), U73122 (phospholipase C), 2-APB (IP3-receptors) or with TPPO (Trpm5, transient receptor potential-melastatin 5 channel) reduced the denatonium effect. Supportively, the ISC was also diminished in Trpm5−/− mice. Mecamylamine (nicotinic acetylcholine receptor, nAChR, inhibitor) and amiloride (epithelial sodium channel, ENaC, antagonist) decreased the denatonium effect. Additionally, the inhibition of Gα subunits (pertussis toxin) reduced the denatonium effect, while an inhibition of phosphodiesterase (IBMX) increased and of adenylate cyclase (forskolin) reversed the denatonium effect. The cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh172 and the KCNQ1 potassium channel antagonist chromanol 293B both reduced the denatonium effect. Thus, denatonium reduces ISC via the canonical bitter taste signalling cascade leading to the Trpm5-dependent nAChR-mediated inhibition of ENaC as well as Gα signalling leading to a reduction in cAMP-dependent ISC. Therefore, BC activation contributes to the regulation of fluid homeostasis.

Sweet taste perception in mice is blunted by PTBP1-regulated skipping of Tas1r2 exon 4.

Taste perception, initiated by activation of taste receptors in taste bud cells, is crucial for regulating nutrient intake. Genetic polymorphisms in taste receptor genes cannot fully explain the wide individual variations of taste sensitivity. Alternative splicing (AS) is a ubiquitous posttranscriptional mode of gene regulation that enriches the functional diversity of proteins. Here, we report the identification of a novel splicing variant of sweet taste receptor gene Tas1r2 (Tas1r2_∆e4) in mouse taste buds and the mechanism by which it diminishes sweet taste responses in vitro and in vivo. Skipping of Tas1r2 exon 4 in Tas1r2_∆e4 led to loss of amino acids in the extracellular Venus flytrap domain, and the truncated isoform reduced the response of sweet taste receptors (STRs) to all sweet compounds tested by generating nonfunctional T1R2/T1R3 STR heterodimers. The splicing factor PTBP1 (polypyrimidine tract-binding protein 1) promoted Tas1r2_∆e4 generation through binding to a polypyrimidine-rich splicing silencer in Tas1r2 exon 4, thus decreasing STR function and sweet taste perception in mice. Taken together, these data reveal the existence of a regulated AS event in Tas1r2 expression and its effect on sweet taste perception, providing a novel mechanism for modulating taste sensitivity at the posttranscriptional level.

Activation of specific bitter taste receptors by olive oil phenolics and secoiridoids

Extra-virgin olive oil (EVOO) is a critical component of the Mediterranean diet, which has been found beneficial to human health. Bitterness is often positively associated with the presence of phenolic compounds in EVOO. There are twenty-five bitter taste receptors (TAS2Rs) in humans, each of which responds to specific bitter tastants. The identity of phenolic compounds and the bitter taste receptors they stimulate remain unknown. In this study, we isolated 12 phenolic and secoiridoid compounds from the olive fruit and the oil extracted from it, and tested their ability to stimulate bitter taste receptor activity, using a calcium mobilization functional assay. Our results showed that seven out of twelve studied compounds activated TAS2R8, and five of them activated TAS2R1, TAS2R8, and TAS2R14. The phenolic compounds oleuropein aglycon and ligstroside aglycon were the most potent bitter tastants in olive oil. TAS2R1 and TAS2R8 were the major bitter taste receptors activated most potently by these phenolic compounds. The results obtained here could be utilized to predict and control the bitterness of olive oil based on the concentration of specific bitter phenolics produced during the milling process of olives.

Bitter Taste Receptors Expression in Human Granulosa and Cumulus Cells: New Perspectives in Female Fertility.

Bitter taste receptors (TAS2RS) expression is not restricted to the oral cavity and the presence of these receptors in the male reproductive system and sperm provides insights into their possible role in human reproduction. To elucidate the potential role of TAS2Rs in the female reproductive system, we investigated the expression and localization of bitter taste receptors and the components of signal transduction cascade involved in the pathway of taste receptors in somatic follicular cells obtained from women undergoing assisted reproductive techniques. We found that TAS2R genes are expressed in both cumulus (CCs) and granulosa (GCs) cells, with TAS2R14 being the most highly expressed bitter receptor subtype. Interestingly, a slight increase in the expression of TAS2R14 and TAS2R43 was shown in both GCs and CCs in young women (p < 0.05), while a negative correlation may be established between the number of oocytes collected at the pickup and the expression of TAS2R43. Regarding α-gustducin and α-transducin, two Gα subunits expressed in the taste buds on the tongue, we provide evidence for their expression in CCs and GCs, with α-gustducin showing two additional isoforms in GCs. Finally, we shed light on the possible downstream transduction pathway initiated by taste receptor activation in the female reproductive system. Our study, showing for the first time the expression of taste receptors in the somatic ovarian follicle cells, significantly extends the current knowledge of the biological role of TAS2Rs for human female fertility.