Journal articles on the topic 'Bitter taster receptor'
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Feeney, E., S. O'Brien, A. Scannell, A. Markey, and E. R. Gibney. "Genetic variation in taste perception: does it have a role in healthy eating?" Proceedings of the Nutrition Society 70, no. 1 (November 22, 2010): 135–43. http://dx.doi.org/10.1017/s0029665110003976.
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Taste is often cited as the factor of greatest significance in food choice, and has been described as the body's ‘nutritional gatekeeper’. Variation in taste receptor genes can give rise to differential perception of sweet, umami and bitter tastes, whereas less is known about the genetics of sour and salty taste. Over twenty-five bitter taste receptor genes exist, of which TAS2R38 is one of the most studied. This gene is broadly tuned to the perception of the bitter-tasting thiourea compounds, which are found in brassica vegetables and other foods with purported health benefits, such as green tea and soya. Variations in this gene contribute to three thiourea taster groups of people: supertasters, medium tasters and nontasters. Differences in taster status have been linked to body weight, alcoholism, preferences for sugar and fat levels in food and fruit and vegetable preferences. However, genetic predispositions to food preferences may be outweighed by environmental influences, and few studies have examined both. The Tastebuddies study aimed at taking a holistic approach, examining both genetic and environmental factors in children and adults. Taster status, age and gender were the most significant influences in food preferences, whereas genotype was less important. Taster perception was associated with BMI in women; nontasters had a higher mean BMI than medium tasters or supertasters. Nutrient intakes were influenced by both phenotype and genotype for the whole group, and in women, the AVI variation of the TAS2R38 gene was associated with a nutrient intake pattern indicative of healthy eating.
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Abrol, Ravinder, Jun Tan, Hongxiang Hui, William A. Goddard III, and Stephen J. Pandol. "Structural basis for bitter taste receptor activation and its potential role in targeting diabetes." Functional Foods in Health and Disease 5, no. 3 (March 18, 2015): 117. http://dx.doi.org/10.31989/ffhd.v5i3.176.
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Background: Taste receptors are G protein-coupled receptors that, besides being present in the taste buds, have also been shown to be present in the gastrointestinal (GI) system, respiratory system, and brain, though their function at these locations is not well understood.Objective: To understand the nutrient mediated release of gut peptides like GLP-1 from enteroendocrine L-cells of the GI system, we focused on a bitter taste receptor TAS2R38 (based on animal models) to investigate the structural basis of its potential role in the release of gut peptides. Methods: The atomic-level structure of bitter taste receptor TAS2R38 was predicted using GEnSeMBLE, a first-principle based GPCR structure prediction method. These structures were obtained for the dominant taster haplotype (PAV) as well as for the nontaster haplotype (AVI) of the receptor. The known ligands phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PTU) were docked to these structures to provide a structural basis for the taster and nontaster haplotypes.Results: Docking of known ligands PTU and PTC to taster and nontaster haplotypes of the bitter taste receptor showed a backbone hydrogen bond to residue 262 in taster but not in nontaster haplotype, suggesting a potential mode of action of these molecules in the activation of the bitter taste receptor. Conclusion: These results, combined with the ability of PTC to release gut peptides from in vitro models of the enteroendocrine L-cells, suggest a potential structural basis for TAS2R38 activation that can lead to the release of those peptides. This release has a therapeutic benefit for type 2 diabetes and implies a role for bitter tasting (but safe) natural compounds targeting TAS2R38 as potential drug candidates for curing type 2 diabetes.Key words: TAS2R38, GLP-1 release, PYY release, CCK release, enteroendocrine L cell, GPCR, protein structure prediction, GEnSeMBLE
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Pilic, Leta, Catherine Anna-Marie Graham, Nisrin Hares, Megan Brown, Jonathan Kean, Yasmin Wehliye, Ella McGrigor, et al. "Bitter Taste Sensitivity Is Determined by TAS2R38 Haplotype, Associated with Saturated Fat Intake and Is Lower in Overweight and Obese Compared to Normal Weight UK adults." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1271. http://dx.doi.org/10.1093/cdn/nzaa058_029.
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Abstract Objectives Taste perception (sensitivity) may be determined by genetic variations in taste receptors and it affects food intake. Lower fat taste sensitivity is associated with higher dietary fat intake and body mass index (BMI). Recently, associations between bitter and fat taste sensitivity have been reported whereby bitter taste perception may be involved in textural perception of dietary fat. However, it is not clear if lower sensitivity to bitter taste would lead to an actual higher fat intake. Our objectives were to explore the associations between haplotypes in the bitter taste receptor TAS2R38, bitter taste sensitivity and fat intake and if bitter taste sensitivity is lower in individuals with higher BMI. Methods Ethical approval was obtained from the St Mary's and Oxford Brookes University Ethics Committee. Eighty-eight healthy Caucasian participants (44% male and 56% female; mean BMI 24.9 ± 4.8 kg/m2 and mean age 35 ± 14 years) completed this cross-sectional study. Height and weight were measured and genotyping performed for rs713598, rs1726866, rs10246939 genetic variants in the TAS2R38. Haplotypes were determined with Haploview software. Participants rated the intensity of a phenylthiocarbamide (PTC) impregnated strip on the general Labelled Magnitude Scale (gLMS) to determine bitter taste sensitivity and were classified as bitter tasters and non-tasters. Dietary fat intake was calculated from the EPIC-Norfolk Food Frequency Questionnaire and expressed as % total energy intake. Results TAS2R38 haplotypes were associated with bitter taster status (P < 0.005). PTC ratings of intensity were negatively correlated with % saturated fat (SFA) intake (rs = −0.256, P = 0.016). %SFA and %total fat (rs = 0.656, P < 0.005) and %total fat and energy intake (kcal) (rs = 0.225, P = 0.035) were positively correlated. Normal weight participants rated PTC strips as more intense compared to overweight and obese participants (mean rank 53 vs. 41, P = 0.033). Conclusions Bitter taste perception is determined by genetics and lower sensitivity to this taste is associated with higher intake of SFA. Lower bitter taste sensitivity in overweight/obese participants suggests that impaired bitter taste may be associated with an overall unhealthier and more energy dense dietary pattern. Funding Sources St Mary's and Oxford Brookes University.
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Biró, Barbara, Dániel Koren, Adrienn Lichthammer, Márta Veresné Bálint, Attila Gere, and Zoltán Kókai. "Relationships amongst phenyltiocarbamide sensitivity, body composition, coffee and tea consumption." Élelmiszervizsgálati Közlemények 68, no. 2 (2022): 3855–65. http://dx.doi.org/10.52091/evik-2022/2-1-eng.
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Polymorphisms of TAS2R38 gene responsible for bitter taste perception elicit a bimodal receptor response in the population upon the detection of phenylthiocarbamide and 6-n-propylthiouracil, respectively. Genetic differences in sensitivity to phenylthiocarbamide and 6-n-propylthiouracil may affect body composition, food preferences, and frequency of consuming different food types. To date, no publication has been published in Hungary on the joint study of these factors. The aim of the present research is to find correlations between phenylthiocarbamide taster status and body composition, and the frequency of consumption of different bitter-tasting foods. In the study, a taster status survey of participants (n = 170), a bioimpedance-based body composition analysis (n = 96) and completed a food frequency questionnaire of bitter foods (n = 170) were conducted. Descriptive statistical methods, cross-tabulation analysis, multiple correspondence analysis, and Mann-Whitney test were used for data analysis at 5% significance level. The proportions of the taster and non-taster categories proved to be the same as reported by international literature (70%/30% respectively). There were no significant correlations among taster status and the other examined parameters, however, based on the multiple correspondence analysis, the observed trends are in accordance with the international literature. There were significant correlations among gender, body composition and some variables describing food preference. Based on the literature data and our own results, there can be a relationship between genotype and body composition, and genotype and food choice. Further analyses with large-sample size and representative research are needed to substantiate these assumptions.
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Ergün, Can, and Meral Aksoy. "Relationships between the hTAS2R38 genotype, food choice, and anthropometric variables in normal-weighted and overweight adults." Genetika 45, no. 2 (2013): 381–91. http://dx.doi.org/10.2298/gensr1302381e.
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Aim: Taste is a major determinant of food choice; however, there is a great lack of knowledge about how taste perception affects human nutrition. Bitter taste perception presents unique opportunities for investigating this subject. The aim of this study was to determine whether polymorphisms on the bitter taste receptor gene hTAS2R38 affect an individual?s food choices and some anthropometric variables. Subjects and Method: In this study, the possible relationship between food preferences, body weight, and polymorphisms on hTAS2R38 was investigated in healthy volunteers (n=178) who weighed within the normal range (BMI: 20-24.9 kg/m2, n=90) and those who were overweight, but otherwise healthy (BMI ? 25.0 kg/m2, n=88). Descriptive information about the subjects was collected via a questionnaire, and anthropometric measurements were taken by the researcher. Records of three consecutive days of food consumption were collected to determine each subject?s macronutrient intake. For identification of the hTAS2R38 genotype, samples were taken from each participant's in-mouth epithelial cell line, and the genetic material was analyzed at the laboratory for Rs713598. Results: The percentage of ?non-tasters? (n=42) among the whole population was 23.6% (C-Homozygote: 23.6%) while ?tasters? (n=136) comprised 76.4% (CG-Heterozygote: 46.6%, G-Homozygote: 29.8%). When group-wide and between-group comparisons were made, it was revealed that taster status didn?t affect differences in anthropometric measures. Detected differences in macronutrient intake were due to gender. Discussion: Polymorphisms on hTAS2R38 bitter taste receptor gene had no effect on variables such as body weight, anthropometric variables, body fat percentage, or food choices within the study population.
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INOUE, MASASHI, XIA LI, STUART A. McCAUGHEY, GARY K. BEAUCHAMP, and ALEXANDER A. BACHMANOV. "Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate." Physiological Genomics 5, no. 4 (April 27, 2001): 181–86. http://dx.doi.org/10.1152/physiolgenomics.2001.5.4.181.
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In mice, behavioral acceptance of the bitter compound sucrose octaacetate (SOA) depends on allelic variation of a single gene, Soa. The SW.B6- Soabcongenic mouse strain has the genetic background of an “SOA taster” SWR/J strain and an Soa-containing donor chromosome fragment from an “SOA nontaster” C57BL/6J strain. Using microsatellite markers polymorphic between the two parental strains, we determined that the donor fragment spans 5–10 cM of distal chromosome 6. The SWR/J mice avoided SOA in two-bottle tests with water and had strong responses to SOA in two gustatory nerves, the chorda tympani (CT) and glossopharyngeal (GL). In contrast, the SW.B6- Soab mice were indifferent to SOA in two-bottle tests and had very weak responses to SOA in both of these nerves. The SWR/J and SW.B6- Soab mice did not differ in responses of either nerve to sucrose, NaCl, HCl, or the bitter-tasting stimuli quinine, denatonium, strychnine, 6- n-propylthiouracil, phenylthiocarbamide, and MgSO4. Thus the effect of the Soa genotype on SOA avoidance is mediated by peripheral taste responsiveness to SOA, involving taste receptor cells innervated by both the CT and GL nerves.
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Taha, Mohamed A., Christian A. Hall, Colin J. Shortess, Richard F. Rathbone, and Henry P. Barham. "Treatment Protocol for COVID-19 Based on T2R Phenotype." Viruses 13, no. 3 (March 18, 2021): 503. http://dx.doi.org/10.3390/v13030503.
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COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/− hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients’ T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype.
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Deshaware, Shweta, and Rekha Singhal. "Genetic variation in bitter taste receptor gene TAS2R38 , PROP taster status and their association with body mass index and food preferences in Indian population." Gene 627 (September 2017): 363–68. http://dx.doi.org/10.1016/j.gene.2017.06.047.
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Lemon, Christian H., and David V. Smith. "Neural Representation of Bitter Taste in the Nucleus of the Solitary Tract." Journal of Neurophysiology 94, no. 6 (December 2005): 3719–29. http://dx.doi.org/10.1152/jn.00700.2005.
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Based on the molecular findings that many bitter taste receptors (T2Rs) are expressed within the same receptor cells, it has been proposed that bitter taste is encoded by the activation of discrete neural elements. Here we examined how a variety of bitter stimuli are represented by neural activity in central gustatory neurons. Taste responses (spikes/s) evoked by bathing the tongue and palate with intensity-matched concentrations (in M) of 2 sugars (0.32 sucrose and 0.5 D-fructose), ethanol (40%), 4 salts (0.01 NaCl, 0.008 NaNO3, 0.01 MgCl2, and 0.05 KCl), 2 acids (0.003 HCl and 0.005 citric acid), and 10 bitter ligands (0.007 quinine-HCl, 0.015 denatonium benzoate, 0.003 l-cysteine, 0.001 nicotine, 0.005 strychnine-HCl, 0.04 tetraethylammonium chloride, 0.03 atropine-SO4, 0.005 brucine-SO4, 0.03 papaverine-HCl, and 0.009 sparteine) were recorded from 51 neurons in the nucleus of the solitary tract of anesthetized rats. Cluster analysis was used to categorize neurons into types based on responses to sucrose, NaCl, HCl, and quinine-HCl. Three groupings emerged: type S (responded optimally to sweets), type N (sodium-optimal), and type H/Q (responded robustly to bitters, acids, and salts). Multivariate analyses revealed that across-neuron patterns of response among bitter stimuli were strongly correlated. However, neural type H/Q, which was most responsive to bitter tastants, was not differentially sensitive to bitter stimuli and Na+ salts, which rats perceive as distinct. Thus central neurons most responsive to bitter substances receive significant input from receptors that mediate other tastes, indicating that bitter stimuli are not represented by activity in specifically tuned neurons.
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Schiffman, SS. "Taste Transduction and Modulation." Physiology 3, no. 3 (June 1, 1988): 109–12. http://dx.doi.org/10.1152/physiologyonline.1988.3.3.109.
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The application to the tongue of agents that interact with taste cells can tell us a great deal about transduction mechanisms that mediate taste. Separate pathways for Na+ and K+ appear to be part of the transduction mechanisms for the tastes of sodium and potassium salts. Caffeine and other methyl xanthines can potentiate certain tastes;this enhancement may involve the interaction of caffeine with an adenosine receptor. There is also evidence for glutamate and inosine receptors in addition to multiple receptors for sweet and bitter tastes.
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Hartley, Isabella, Djin Liem, and Russell Keast. "Umami as an ‘Alimentary’ Taste. A New Perspective on Taste Classification." Nutrients 11, no. 1 (January 16, 2019): 182. http://dx.doi.org/10.3390/nu11010182.
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Applied taste research is increasingly focusing on the relationship with diet and health, and understanding the role the sense of taste plays in encouraging or discouraging consumption. The concept of basic tastes dates as far back 3000 years, where perception dominated classification with sweet, sour, salty, and bitter consistently featuring on basic taste lists throughout history. Advances in molecular biology and the recent discovery of taste receptors and ligands has increased the basic taste list to include umami and fat taste. There is potential for a plethora of other new basic tastes pending the discovery of taste receptors and ligands. Due to the possibility for an ever-growing list of basic tastes it is pertinent to critically evaluate whether new tastes, including umami, are suitably positioned with the four classic basic tastes (sweet, sour, salty, and bitter). The review critically examines the evidence that umami, and by inference other new tastes, fulfils the criteria for a basic taste, and proposes a subclass named ‘alimentary’ for tastes not meeting basic criteria.
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Yoshida, Ryusuke, and Yuzo Ninomiya. "Taste information derived from T1R-expressing taste cells in mice." Biochemical Journal 473, no. 5 (February 24, 2016): 525–36. http://dx.doi.org/10.1042/bj20151015.
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The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination.
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Riera, Céline E., Horst Vogel, Sidney A. Simon, and Johannes le Coutre. "Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 293, no. 2 (August 2007): R626—R634. http://dx.doi.org/10.1152/ajpregu.00286.2007.
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Throughout the world many people use artificial sweeteners (AS) for the purpose of reducing caloric intake. The most prominently used of these molecules include saccharin, aspartame (Nutrasweet), acesulfame-K, and cyclamate. Despite the caloric advantage they provide, one key concern in their use is their aversive aftertaste that has been characterized on a sensory level as bitter and/or metallic. Recently, it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. To more fully understand the biology behind these phenomena we have addressed the question of whether AS could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the AS aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca2+ imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons, we find that in both systems, AS activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. We also found that TRPV1 receptors are activated by CuSO4, ZnSO4, and FeSO4, three salts known to produce a metallic taste sensation. In summary, our results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.
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Tordoff, Michael G., and Hillary T. Ellis. "Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene." Physiological Genomics 45, no. 18 (September 15, 2013): 834–55. http://dx.doi.org/10.1152/physiolgenomics.00092.2013.
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The BTBR T+ tf/J (BTBR) mouse strain is indifferent to exemplars of sweet, Polycose, umami, bitter, and calcium tastes, which share in common transduction by G protein-coupled receptors (GPCRs). To investigate the genetic basis for this taste dysfunction, we screened 610 BTBR × NZW/LacJ F2 hybrids, identified a potent QTL on chromosome 17, and isolated this in a congenic strain. Mice carrying the BTBR/BTBR haplotype in the 0.8-Mb (21-gene) congenic region were indifferent to sweet, Polycose, umami, bitter, and calcium tastes. To assess the contribution of a likely causative culprit, Itpr3, the inositol triphosphate receptor 3 gene, we produced and tested Itpr3 knockout mice. These were also indifferent to GPCR-mediated taste compounds. Sequencing the BTBR form of Itpr3 revealed a unique 12 bp deletion in Exon 23 (Chr 17: 27238069; Build 37). We conclude that a spontaneous mutation of Itpr3 in a progenitor of the BTBR strain produced a heretofore unrecognized dysfunction of GPCR-mediated taste transduction.
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McMullen, Michael K. "Neural Transmission from Oropharyngeal Bitter Receptors to the Medulla is Partially or Completely Labelled-Line." Natural Product Communications 11, no. 8 (August 2016): 1934578X1601100. http://dx.doi.org/10.1177/1934578x1601100841.
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The ground breaking advances in taste cell receptor cell physiology over the last 20 years have established a functional basis which enables neural pathways to be mapped. There is only one, or perhaps several, types of taste receptors for salt, sour, sweet and umami (meaty) tastes and stimulation of each receptor type elicits responses in different cognitive regions. These findings support the labelled-line neural pathway model. In contrast, there are 25 types of the bitter taste receptors which all produce the same cognitive sensation, a finding which supports the across-fiber pattern model. This paper compiles the findings of several human studies investigating the impact of bitter tastants on postprandial hemodynamics, to demonstrate that diverse bitter tastants are capable of eliciting a range of characteristic reflex cephalic phase responses in the autonomic and cardiovascular systems. These findings indicate that neural pathways from the oropharyngeal bitter taste receptors to the nucleus of the solitary tract are either partially or completely labelled-line. Consequently, the hedonics of a bitter tastant are not an accurate indicator of the cephalic phase responses elicited by the tastant. The finding that secondary metabolites present in dietary condiments modulate autonomic activity and in particular postprandial hemodynamics is novel and adds a new dimension to our understanding of the ways in which humans are influenced by their diet, both in health and disease. These findings suggest that condiments play a role in food digestion, unrelated to their hedonistic qualities. Consequently, condiments may be of significance to those with digestive disorders and especially for diabetics experiencing gastroparesis and/or postprandial hypotension. Additionally, the findings suggest a noninvasive method to assess the integrity of multiple neural pathways. For investigators exploring the effect of condiments on autonomic reflexes, traditional cuisines may be a valuable source as they are full of uncharted human recordings.
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Zhao, Wenzhu, Donghui Li, Yingxue Wang, Ruotong Kan, Huizhuo Ji, Lijun Su, Zhipeng Yu, and Jianrong Li. "Identification and molecular docking of peptides from Mizuhopecten yessoensis myosin as human bitter taste receptor T2R14 blockers." Food & Function 12, no. 23 (2021): 11966–73. http://dx.doi.org/10.1039/d1fo02447g.
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Jeruzal-Świątecka, Joanna, Wojciech Fendler, and Wioletta Pietruszewska. "Clinical Role of Extraoral Bitter Taste Receptors." International Journal of Molecular Sciences 21, no. 14 (July 21, 2020): 5156. http://dx.doi.org/10.3390/ijms21145156.
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Humans can recognise five basic tastes: sweet, sour, salty, bitter and umami. Sour and salty substances are linked to ion channels, while sweet, bitter and umami flavours are transmitted through receptors linked to the G protein (G protein-coupled receptors; GPCRs). There are two main types of GPCRs that transmit information about sweet, umami and bitter tastes—the Tas1r and TAS2R families. There are about 25 functional TAS2R genes coding bitter taste receptor proteins. They are found not only in the mouth and throat, but also in the intestines, brain, bladder and lower and upper respiratory tract. The determination of their purpose in these locations has become an inspiration for much research. Their presence has also been confirmed in breast cancer cells, ovarian cancer cells and neuroblastoma, revealing a promising new oncological marker. Polymorphisms of TAS2R38 have been proven to have an influence on the course of chronic rhinosinusitis and upper airway defensive mechanisms. TAS2R receptors mediate the bronchodilatory effect in human airway smooth muscle, which may lead to the creation of another medicine group used in asthma or chronic obstructive pulmonary disease. The discovery that functionally compromised TAS2R receptors negatively impact glucose homeostasis has produced a new area of diabetes research. In this article, we would like to focus on what facts have been already established in the matter of extraoral TAS2R receptors in humans.
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Delompré, Thomas, Christine Belloir, Christophe Martin, Christian Salles, and Loïc Briand. "Detection of Bitterness in Vitamins Is Mediated by the Activation of Bitter Taste Receptors." Nutrients 14, no. 19 (October 5, 2022): 4141. http://dx.doi.org/10.3390/nu14194141.
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Vitamins are known to generate bitterness, which may contribute to an off-taste or aftertaste for some nutritional supplements. This negative sensation can lead to a reduction in their consumption. Little is known about the bitter taste threshold and taste sensing system for the bitter taste detection of vitamins. To better understand the mechanisms involved in bitterness perception, we combined taste receptor functional assays and sensory analysis. In humans, bitter taste detection is mediated by 25 G-protein-coupled receptors belonging to the TAS2R family. First, we studied the bitterness of thirteen vitamins using a cellular-based functional taste receptor assay. We found four vitamins that can stimulate one or more TAS2Rs. For each positive molecule–receptor combination, we tested seven increasing concentrations to determine the half-maximal effective concentration (EC50) and the cellular bitter taste threshold. Second, we measured the bitter taste detection threshold for four vitamins that exhibit a strong bitter taste using a combination of ascending series and sensory difference tests. A combination of sensory and biological data can provide useful results that explain the perception of vitamin bitterness and its real contribution to the off-taste of nutritional supplements.
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Carey, Ryan M., and Robert J. Lee. "Taste Receptors in Upper Airway Innate Immunity." Nutrients 11, no. 9 (August 28, 2019): 2017. http://dx.doi.org/10.3390/nu11092017.
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Taste receptors, first identified on the tongue, are best known for their role in guiding our dietary preferences. The expression of taste receptors for umami, sweet, and bitter have been demonstrated in tissues outside of the oral cavity, including in the airway, brain, gastrointestinal tract, and reproductive organs. The extra-oral taste receptor chemosensory pathways and the endogenous taste receptor ligands are generally unknown, but there is increasing data suggesting that taste receptors are involved in regulating some aspects of innate immunity, and may potentially control the composition of the nasal microbiome in healthy individuals or patients with upper respiratory diseases like chronic rhinosinusitis (CRS). For this reason, taste receptors may serve as potential therapeutic targets, providing alternatives to conventional antibiotics. This review focuses on the physiology of sweet (T1R) and bitter (T2R) taste receptors in the airway and their activation by secreted bacterial products. There is particular focus on T2R38 in sinonasal ciliated cells, as well as the sweet and bitter receptors found on specialized sinonasal solitary chemosensory cells. Additionally, this review explores the impact of genetic variations in these receptors on the differential susceptibility of patients to upper airway infections, such as CRS.
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McMahon, Derek B., Jennifer F. Jolivert, Li Eon Kuek, Nithin D. Adappa, James N. Palmer, and Robert J. Lee. "Utilizing the Off-Target Effects of T1R3 Antagonist Lactisole to Enhance Nitric Oxide Production in Basal Airway Epithelial Cells." Nutrients 15, no. 3 (January 19, 2023): 517. http://dx.doi.org/10.3390/nu15030517.
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Human airway sweet (T1R2 + T1R3), umami (T1R1 + T1R3), and bitter taste receptors (T2Rs) are critical components of the innate immune system, acting as sensors to monitor pathogenic growth. T2Rs detect bacterial products or bitter compounds to drive nitric oxide (NO) production in both healthy and diseased epithelial cell models. The NO enhances ciliary beating and also directly kills pathogens. Both sweet and umami receptors have been characterized to repress bitter taste receptor signaling in healthy and disease models. We hypothesized that the sweet/umami T1R3 antagonist lactisole may be used to alleviate bitter taste receptor repression in airway basal epithelial cells and enhance NO production. Here, we show that lactisole activates cAMP generation, though this occurs through a pathway independent of T1R3. This cAMP most likely signals through EPAC to increase ER Ca2+ efflux. Stimulation with denatonium benzoate, a bitter taste receptor agonist which activates largely nuclear and mitochondrial Ca2+ responses, resulted in a dramatically increased cytosolic Ca2+ response in cells treated with lactisole. This cytosolic Ca2+ signaling activated NO production in the presence of lactisole. Thus, lactisole may be useful coupled with bitter compounds as a therapeutic nasal rinse or spray to enhance beneficial antibacterial NO production in patients suffering from chronic inflammatory diseases such as chronic rhinosinusitis.
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Tizzano, Marco, and Thomas E. Finger. "Chemosensors in the Nose: Guardians of the Airways." Physiology 28, no. 1 (January 2013): 51–60. http://dx.doi.org/10.1152/physiol.00035.2012.
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The G-protein-coupled receptor molecules and downstream effectors that are used by taste buds to detect sweet, bitter, and savory tastes are also utilized by chemoresponsive cells of the airways to detect irritants. Here, we describe the different cell types in the airways that utilize taste-receptor signaling to trigger protective epithelial and neural responses to potentially dangerous toxins and bacterial infection.
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Mineev, V. N., M. A. Nyoma, L. N. Sorokina, P. V. Bryukhanova, and D. E. Koksharova. "Gustometry in various variants of bronchial asthma: Sensitivity thresholds for bitter and sweet tast." Medical Immunology (Russia) 23, no. 1 (March 1, 2021): 117–26. http://dx.doi.org/10.15789/1563-0625-giv-2070.
Full textAbstract:
The first studies were published on the possible pathogenetic role of so-called ectopically localized taste receptors in bronchial asthma. The receptors for bitter and sweet taste, may, apparently, have opposite functions, but in available literature there is no data on the balance of sensitivity for bitter and sweet tastes in the same patients with bronchial asthma. The aim of the present work is to simultaneously assess the sensitivity of canonical lingual receptors to bitter and sweet taste in the same patients with different clinical variants of bronchial asthma by methods applicable in wide clinical practice. 16 healthy persons and 35 patients with bronchial asthma were examined at the M.V. Chernorutsky Clinics of Hospital Therapy at First St. Petersburg State I. Pavlov Medical University. The sensitivity for bitter taste was assessed using The Frey Scientific 569885 PTC Taste Paper test strip kit containing phenylthiourea solution. Sucrose solutions at concentrations of 0.3; 0,4; 0,5; 0,6; 0,7; 0,8; 0,9 % for determination of individual value of taste thresholds to sweet taste were used. The bitter-to-sweet taste sensitivity balance was assessed on the basis of an original “bitter/sweet taste sensitivity” index. The highest values of index of bitter/sweet taste was found in the allergic variant of bronchial asthma: its values are significantly different from those in healthy persons only at low sucrose concentrations (0.3-0.4%). The factor analysis revealed an association between taste imbalance (a shift towards high sensitivity to sweet taste) and key characteristics of bronchial asthma, including severity of bronchial asthma course, duration of inhaled glucocorticosteroid use and inefficiency of β2-agonists use at pre-clinical stage. It has been revealed by gustometry that in the allergic variant of bronchial asthma there is a decreased sensitivity for bitter test substance (phenylthiourea), along with higher sensitivity for sweet taste (sucrose).
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Lipchock, Sarah V., Andrew I. Spielman, Julie A. Mennella, Corrine J. Mansfield, Liang-Dar Hwang, Jennifer E. Douglas, and Danielle R. Reed. "Caffeine Bitterness is Related to Daily Caffeine Intake and Bitter Receptor mRNA Abundance in Human Taste Tissue." Perception 46, no. 3-4 (January 24, 2017): 245–56. http://dx.doi.org/10.1177/0301006616686098.
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We investigated whether the abundance of bitter receptor mRNA expression from human taste papillae is related to an individual’s perceptual ratings of bitter intensity and habitual intake of bitter drinks. Ratings of the bitterness of caffeine and quinine and three other bitter stimuli (urea, propylthiouracil, and denatonium benzoate) were compared with relative taste papilla mRNA abundance of bitter receptors that respond to the corresponding bitter stimuli in cell-based assays ( TAS2R4, TAS2R10, TAS2R38, TAS2R43, and TAS2R46). We calculated caffeine and quinine intake from a food frequency questionnaire. The bitterness of caffeine was related to the abundance of the combined mRNA expression of these known receptors, r = 0.47, p = .05, and self-reported daily caffeine intake, t(18) = 2.78, p = .012. The results of linear modeling indicated that 47% of the variance among subjects in the rating of caffeine bitterness was accounted for by these two factors (habitual caffeine intake and taste receptor mRNA abundance). We observed no such relationships for quinine but consumption of its primary dietary form (tonic water) was uncommon. Overall, diet and TAS2R gene expression in taste papillae are related to individual differences in caffeine perception.
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Xu, Weixiu, Lijie Wu, Shenhui Liu, Xiao Liu, Xiaoling Cao, Cui Zhou, Jinyi Zhang, et al. "Structural basis for strychnine activation of human bitter taste receptor TAS2R46." Science 377, no. 6612 (September 16, 2022): 1298–304. http://dx.doi.org/10.1126/science.abo1633.
Full textAbstract:
Taste sensing is a sophisticated chemosensory process, and bitter taste perception is mediated by type 2 taste receptors (TAS2Rs), or class T G protein–coupled receptors. Understanding the detailed molecular mechanisms behind taste sensation is hindered by a lack of experimental receptor structures. Here, we report the cryo–electron microscopy structures of human TAS2R46 complexed with chimeric mini–G protein gustducin, in both strychnine-bound and apo forms. Several features of TAS2R46 are disclosed, including distinct receptor structures that compare with known GPCRs, a new “toggle switch,” activation-related motifs, and precoupling with mini–G protein gustducin. Furthermore, the dynamic extracellular and more-static intracellular parts of TAS2R46 suggest possible diverse ligand-recognition and activation processes. This study provides a basis for further exploration of other bitter taste receptors and their therapeutic applications.
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Sihombing, Monang, and Victoria Kristina Ananingsih. "Encapsulated Curcuma aeruginosa: Inhibition Method of Bitter Receptor Cells from The Perspective of Wall Formation." Indonesian Journal of Agricultural Research 1, no. 2 (September 3, 2018): 172–78. http://dx.doi.org/10.32734/injar.v1i2.267.
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Curcuma aeruginosa is one of the herbs with health benefits and has been used in traditional medicine, has the characteristic bitter taste, so that limited use was. The formation of walls in the active component coating process can minimize direct contact of bitter receptor cells in the oral peripherals so the perception of bitterness can be reduced. This study used a variation of the WPI concentration as the coating wall materials 10%, 15% and 20%. Formation of coating walls was analyzed using SEM later in the sensory test for effectiveness decreased level of bitterness. The addition of 10% WPI results in the best wall formation was in Curcuma aeruginosa, which could decrease perception of significant bitterness. In contrast to the addition of WPI 15% and 20% were found in an oval shape, craters and ruptures form on coating wall, reducing the protection of the core component and contact with bitter receptor cells in the oral peripheral resulting in bitters taste perception increasing.
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Wooding, Stephen P., Vicente A. Ramirez, and Maik Behrens. "Bitter taste receptors." Evolution, Medicine, and Public Health 9, no. 1 (January 1, 2021): 431–47. http://dx.doi.org/10.1093/emph/eoab031.
Full textAbstract:
Abstract Bitter taste perception plays vital roles in animal behavior and fitness. By signaling the presence of toxins in foods, particularly noxious defense compounds found in plants, it enables animals to avoid exposure. In vertebrates, bitter perception is initiated by TAS2Rs, a family of G protein-coupled receptors expressed on the surface of taste buds. There, oriented toward the interior of the mouth, they monitor the contents of foods, drinks and other substances as they are ingested. When bitter compounds are encountered, TAS2Rs respond by triggering neural pathways leading to sensation. The importance of this role placed TAS2Rs under selective pressures in the course of their evolution, leaving signatures in patterns of gene gain and loss, sequence polymorphism, and population structure consistent with vertebrates' diverse feeding ecologies. The protective value of bitter taste is reduced in modern humans because contemporary food supplies are safe and abundant. However, this is not always the case. Some crops, particularly in the developing world, retain surprisingly high toxicity and bitterness remains an important measure of safety. Bitter perception also shapes health through its influence on preference driven behaviors such as diet choice, alcohol intake and tobacco use. Further, allelic variation in TAS2Rs is extensive, leading to individual differences in taste sensitivity that drive these behaviors, shaping susceptibility to disease. Thus, bitter taste perception occupies a critical intersection between ancient evolutionary processes and modern human health.
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Chen, Xiaoke, Mariano Gabitto, Yueqing Peng, Nicholas J. P. Ryba, and Charles S. Zuker. "A Gustotopic Map of Taste Qualities in the Mammalian Brain." Science 333, no. 6047 (September 1, 2011): 1262–66. http://dx.doi.org/10.1126/science.1204076.
Full textAbstract:
The taste system is one of our fundamental senses, responsible for detecting and responding to sweet, bitter, umami, salty, and sour stimuli. In the tongue, the five basic tastes are mediated by separate classes of taste receptor cells each finely tuned to a single taste quality. We explored the logic of taste coding in the brain by examining how sweet, bitter, umami, and salty qualities are represented in the primary taste cortex of mice. We used in vivo two-photon calcium imaging to demonstrate topographic segregation in the functional architecture of the gustatory cortex. Each taste quality is represented in its own separate cortical field, revealing the existence of a gustotopic map in the brain. These results expose the basic logic for the central representation of taste.
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Henslee, Dillan, Melinda Ellison, Brenda Murdoch, J. Bret Taylor, and Joel Yelich. "PSIV-20 TAS2R genes in sheep and cattle compared to humans." Journal of Animal Science 97, Supplement_3 (December 2019): 229–30. http://dx.doi.org/10.1093/jas/skz258.467.
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Abstract The taste receptor gene family has been extensively studied in human and some genes have been linked to food preferences and addiction; however, research in foraging ruminants is limited. Identification of taste receptor genes in the sheep genome may provide insight regarding individual dietary range plant preferences. Bitter taste has been a large focus of research since Arthur Fox accidentally discovered the bitter tasting compound phenylthiocarbamide (PTC) and observed that bitter taste perception in humans is a variable trait. In theory, individuals who are sensitive to bitter taste will likely consume less bitter tasting foods, which are often antioxidant rich, and be more prone to disease and illness. The objective of this study was to examine known taste receptor genes in sheep and cattle and compare them with humans to determine similarities and differences. Type 2 taste receptors (T2R’s) are the only receptor of the taste gene family to perceive bitterness in foods. Using NCBI genome data viewer, the taste genes were identified on the human (GRCh38.p12), cattle (ARS-UCD1.2), and sheep (Oar_4.0; OORI1) genomes. All 3 species have one T2R gene cluster in common, which includes T2R genes 3, 4, 5, 38, 39, 40, 60, and 41. The span of this cluster is similar for humans (1,457,940 bp), sheep (1,541,593 bp), and cattle (1,594,610 bp). One gene in particular (T2R38) has been associated with PTC sensitivity and linked to aversion of some bitter tasting food in humans. Previous research on T2R38 identified 5 haplotypes, each expressing aversion to bitter taste differently. There is another T2R gene cluster which contains 10 annotated genes in sheep and cattle genomes; however, this region contains an additional 10 genes annotated in the human genome. Understanding genetic variation in TAS2R genes may translate to dietary preferences of sheep grazing on rangelands.
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Maehashi, K., and L. Huang. "Bitter peptides and bitter taste receptors." Cellular and Molecular Life Sciences 66, no. 10 (January 20, 2009): 1661–71. http://dx.doi.org/10.1007/s00018-009-8755-9.
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Fritz, Franziska, Robert Preissner, and Priyanka Banerjee. "VirtualTaste: a web server for the prediction of organoleptic properties of chemical compounds." Nucleic Acids Research 49, W1 (April 27, 2021): W679—W684. http://dx.doi.org/10.1093/nar/gkab292.
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Abstract Taste is one of the crucial organoleptic properties involved in the perception of food by humans. Taste of a chemical compound present in food stimulates us to take in food and avoid poisons. Bitter taste of drugs presents compliance problems and early flagging of potential bitterness of a drug candidate may help with its further development. Similarly, the taste of chemicals present in food is important for evaluation of food quality in the industry. In this work, we have implemented machine learning models to predict three different taste endpoints—sweet, bitter and sour. The VirtualTaste models achieved an overall accuracy of 90% and an AUC of 0.98 in 10-fold cross-validation and in an independent test set. The web server takes a two-dimensional chemical structure as input and reports the chemical's taste profile for three tastes—using molecular fingerprints along with confidence scores, including information on similar compounds with known activity from the training set and an overall radar chart. Additionally, insights into 25 bitter receptors are also provided via target prediction for the predicted bitter compounds. VirtualTaste, to the best of our knowledge, is the first freely available web-based platform for the prediction of three different tastes of compounds. It is accessible via http://virtualtaste.charite.de/VirtualTaste/without any login requirements and is free to use.
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Margolskee, Robert F. "Molecular mechanisms of taste transduction." Pure and Applied Chemistry 74, no. 7 (January 1, 2002): 1125–33. http://dx.doi.org/10.1351/pac200274071125.
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Taste transduction is a specialized form of signal transduction by which taste receptor cells (TRCs) encode at the cellular level information about chemical substances encountered in the oral environment (so-called tastants). Bitter and sweet taste transduction pathways convert chemical information into a cellular second messenger code utilizing cyclic nucleotides, inositol trisphosphate, and/or diacyl glycerol. These messengers are components of signaling cascades that lead to TRC depolarization and Ca++ release. Bitter and sweet taste transduction pathways typically utilize taste-specific or taste-selective seven transmembrane-helix receptors, G proteins, effector enzymes, second messengers, and ion channels. The structural and chemical diversity of tastants has led to the need for multiple transduction mechanisms. Through molecular cloning and data mining, many of the receptors, G proteins, and effector enzymes involved in transducing responses to bitter and sweet compounds are now known. New insights into taste transduction and taste coding underlying sweet and bitter taste qualities have been gained from molecular cloning of the transduction elements, biochemical elucidation of the transduction pathways, electrophysiological analysis of the function of taste cell ion channels, and behavioral analysis of transgenic and knockout models.
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Mizuta, Haruno, Natsuko Kumamoto, Shinya Ugawa, and Takashi Yamamoto. "Additive Effects of L-Ornithine on Preferences to Basic Taste Solutions in Mice." Nutrients 13, no. 11 (October 23, 2021): 3749. http://dx.doi.org/10.3390/nu13113749.
Full textAbstract:
In addition to the taste receptors corresponding to the six basic taste qualities—sweet, salty, sour, bitter, umami, and fatty—another type of taste receptor, calcium-sensing receptor (CaSR), is found in taste-bud cells. CaSR is called the ‘kokumi’ receptor because its agonists increase sweet, salty and umami tastes to induce ‘koku’, a Japanese word meaning the enhancement of flavor characters such as thickness, mouthfulness, and continuity. Koku is an important factor for enhancing food palatability. However, it is not well known whether other kokumi-receptors and substances exist. Here, we show that ornithine (L-ornithine but not D-ornithine) at low concentrations that do not elicit a taste of its own, enhances preferences to sweet, salty, umami, and fat taste solutions in mice. Increased preference to monosodium glutamate (MSG) was the most dominant effect. Antagonists of G-protein-coupled receptor family C group 6 subtype A (GPRC6A) abolished the additive effect of ornithine on MSG solutions. The additive effects of ornithine on taste stimuli are thought to occur in the oral cavity, and are not considered post-oral events because ornithine’s effects were confirmed in a brief-exposure test. Moreover, the additive effects of ornithine and the action of the antagonist were verified in electrophysiological taste nerve responses. Immunohistochemical analysis implied that GPRC6A was expressed in subsets of type II and type III taste cells of mouse circumvallate papillae. These results are in good agreement with those reported for taste modulation involving CaSR and its agonists. The present study suggests that ornithine is a kokumi substance and GPRC6A is a newly identified kokumi receptor.
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Semplici, Bianca, Francesca Paola Luongo, Sofia Passaponti, Claudia Landi, Laura Governini, Giuseppe Morgante, Vincenzo De Leo, Paola Piomboni, and Alice Luddi. "Bitter Taste Receptors Expression in Human Granulosa and Cumulus Cells: New Perspectives in Female Fertility." Cells 10, no. 11 (November 11, 2021): 3127. http://dx.doi.org/10.3390/cells10113127.
Full textAbstract:
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.
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Governini, Laura, Bianca Semplici, Valentina Pavone, Laura Crifasi, Camilla Marrocco, Vincenzo De Leo, Elisabeth Arlt, et al. "Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm." Journal of Clinical Medicine 9, no. 1 (January 18, 2020): 264. http://dx.doi.org/10.3390/jcm9010264.
Full textAbstract:
Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.
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Sainz, Eduardo, Margaret M. Cavenagh, Joanne Gutierrez, James F. Battey, John K. Northup, and Susan L. Sullivan. "Functional characterization of human bitter taste receptors." Biochemical Journal 403, no. 3 (April 12, 2007): 537–43. http://dx.doi.org/10.1042/bj20061744.
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The T2Rs belong to a multi-gene family of G-protein-coupled receptors responsible for the detection of ingested bitter-tasting compounds. The T2Rs are conserved among mammals with the human and mouse gene families consisting of about 25 members. In the present study we address the signalling properties of human and mouse T2Rs using an in vitro reconstitution system in which both the ligands and G-proteins being assayed can be manipulated independently and quantitatively assessed. We confirm that the mT2R5, hT2R43 and hT2R47 receptors respond selectively to micromolar concentrations of cycloheximide, aristolochic acid and denatonium respectively. We also demonstrate that hT2R14 is a receptor for aristolochic acid and report the first characterization of the ligand specificities of hT2R7, which is a broadly tuned receptor responding to strychnine, quinacrine, chloroquine and papaverine. Using these defined ligand–receptor interactions, we assayed the ability of the ligand-activated T2Rs to catalyse GTP binding on divergent members of the Gα family including three members of the Gαi subfamily (transducin, Gαi1 and Gαo) as well as Gαs and Gαq. The T2Rs coupled with each of the three Gαi members tested. However, none of the T2Rs coupled to either Gαs or Gαq, suggesting the T2Rs signal primarily through Gαi-mediated signal transduction pathways. Furthermore, we observed different G-protein selectivities among the T2Rs with respect to both Gαi subunits and Gβγ dimers, suggesting that bitter taste is transduced by multiple G-proteins that may differ among the T2Rs.
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Gulbransen, Brian D., Tod R. Clapp, Thomas E. Finger, and Sue C. Kinnamon. "Nasal Solitary Chemoreceptor Cell Responses to Bitter and Trigeminal Stimulants In Vitro." Journal of Neurophysiology 99, no. 6 (June 2008): 2929–37. http://dx.doi.org/10.1152/jn.00066.2008.
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Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear. Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein α-gustducin, PLCβ2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca2+ ([Ca2+]i). GFP-positive cells respond with increased [Ca2+]i to the bitter receptor ligand denatonium and this response is blocked by the PLC inhibitor U73122. In addition, GFP+ cells respond to the neuromodulators adenosine 5′-triphosphate and acetylcholine but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system.
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Chen, Jingguo, Eric D. Larson, Catherine B. Anderson, Pratima Agarwal, Daniel N. Frank, Sue C. Kinnamon, and Vijay R. Ramakrishnan. "Expression of Bitter Taste Receptors and Solitary Chemosensory Cell Markers in the Human Sinonasal Cavity." Chemical Senses 44, no. 7 (June 20, 2019): 483–95. http://dx.doi.org/10.1093/chemse/bjz042.
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Abstract Some bitter taste receptors (TAS2R gene products) are expressed in the human sinonasal cavity and may function to detect airborne irritants. The expression of all 25 human bitter taste receptors and their location within the upper airway is not yet clear. The aim of this study is to characterize the presence and distribution of TAS2R transcripts and solitary chemosensory cells (SCCs) in different locations of the human sinonasal cavity. Biopsies were obtained from human subjects at up to 4 different sinonasal anatomic sites. PCR, microarray, and qRT-PCR were used to examine gene transcript expression. The 25 human bitter taste receptors as well as the sweet/umami receptor subunit, TAS1R3, and canonical taste signaling effectors are expressed in sinonasal tissue. All 25 human bitter taste receptors are expressed in the human upper airway, and expression of these gene products was higher in the ethmoid sinus than nasal cavity locations. Fluorescent in situ hybridization demonstrates that epithelial TRPM5 and TAS2R38 are expressed in a rare cell population compared with multiciliated cells, and at times, consistent with SCC morphology. Secondary analysis of published human sinus single-cell RNAseq data did not uncover TAS2R or canonical taste transduction transcripts in multiciliated cells. These findings indicate that the sinus has higher expression of SCC markers than the nasal cavity in chronic rhinosinusitis patients, comprising a rare cell type. Biopsies obtained from the ethmoid sinus may serve as the best location for study of human upper airway taste receptors and SCCs.
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Geran, Laura C., and Susan P. Travers. "Single Neurons in the Nucleus of the Solitary Tract Respond Selectively to Bitter Taste Stimuli." Journal of Neurophysiology 96, no. 5 (November 2006): 2513–27. http://dx.doi.org/10.1152/jn.00607.2006.
Full textAbstract:
Molecular data suggest that receptors for all bitter ligands are coexpressed in the same taste receptor cells (TRCs), whereas physiological results indicate that individual TRCs respond to only a subset of bitter stimuli. It is also unclear to what extent bitter-responsive neurons are stimulated by nonbitter stimuli. To explore these issues, single neuron responses were recorded from the rat nucleus of the solitary tract (NST) during whole mouth stimulation with a variety of bitter compounds: 10 μM cycloheximide, 7 mM propylthiouracil, 10 mM denatonium benzoate, and 3 mM quinine hydrochloride at intensities matched for behavioral effectiveness. Stimuli representing the remaining putative taste qualities were also tested. Particular emphasis was given to activating taste receptors in the foliate papillae innervated by the quinine-sensitive glossopharyngeal nerve. This method revealed a novel population of bitter-best (B-best) cells with foliate receptive fields and significant selectivity for bitter tastants. Across all neurons, multidimensional scaling depicted bitter stimuli as loosely clustered yet clearly distinct from nonbitter tastants. When neurons with posterior receptive fields were analyzed alone, bitter stimuli formed a tighter cluster. Nevertheless, responses to bitter stimuli were variable across B-best neurons, with cycloheximide the most, and quinine the least frequent optimal stimulus. These results indicate heterogeneity for the processing of ionic and nonionic bitter tastants, which is dependent on receptive field. Further, they suggest that neurons selective for bitter substances could contribute to taste coding.
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Westermaier, Yvonne. "Taste Perception: Molecular Recognition of Food Molecules." CHIMIA International Journal for Chemistry 75, no. 6 (June 30, 2021): 552–53. http://dx.doi.org/10.2533/chimia.2021.552.
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Molecular recognition of food molecules by ion channels and G-protein coupled receptors is the basis of taste perception. We explore the chemical nature of dietary molecules, and explore how salty, sour, sweet, bitter, and umami tastes can be explained at a molecular level.
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Sincar, Cerasela Dorina, Camelia Ana Grigore, Silvia Martu, Liliana Lacramioara Pavel, Alina Calin, Alina Plesea Condratovici, and Bianca Ioana Chesaru. "Chemical Senses Taste Sensation and Chemical Composition." Materiale Plastice 54, no. 1 (March 30, 2017): 172–74. http://dx.doi.org/10.37358/mp.17.1.4810.
Full textAbstract:
Taste and smell are chemical senses, which means that the receptors (chemoreceptors) of these senses respond to chemical stimuli. In order for a substance to produce a taste sensation, it should be ingested in a solution or subsequently dissolved in saliva; a solid substance put in the mouth perfectly dry is tasteless. Therefore, taste receptors or taste buds occur only on wet surfaces, more precisely in the oral cavity in land vertebrates; however, in aquatic animals, these receptors are scattered all over the body. There are functionally different types of receptors for each of the primary tastes and the distribution of each type is not even on the surface of the tongue mucosa. The sweet and sour sensitive buds are located mainly on the tip of the tongue, those sensitive to acids are located on the sides of the tongue and those stimulated by the bitter taste are located towards the back of the tongue and in the epiglottis area. Taste may be generated by substances which touch the taste buds through the blood; thus, histamine injected intravenously causes a metallic taste, glucin a sweet taste, whereas jaundice may trigger a bitter taste due to the big concentration of gallbladder constituents in the blood.
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Patel, Neil N., Alan D. Workman, and Noam A. Cohen. "Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway." Journal of Pathogens 2018 (October 1, 2018): 1–8. http://dx.doi.org/10.1155/2018/9541987.
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Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.
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Purba, Laurentia Henrieta Permita Sari, Kanthi Arum Widayati, Kei Tsutsui, Nami Suzuki-Hashido, Takashi Hayakawa, Sarah Nila, Bambang Suryobroto, and Hiroo Imai. "Functional characterization of the TAS2R38 bitter taste receptor for phenylthiocarbamide in colobine monkeys." Biology Letters 13, no. 1 (January 2017): 20160834. http://dx.doi.org/10.1098/rsbl.2016.0834.
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Bitterness perception in mammals is mostly directed at natural toxins that induce innate avoidance behaviours. Bitter taste is mediated by the G protein-coupled receptor TAS2R, which is located in taste cell membranes. One of the best-studied bitter taste receptors is TAS2R38, which recognizes phenylthiocarbamide (PTC). Here we investigate the sensitivities of TAS2R38 receptors to PTC in four species of leaf-eating monkeys (subfamily Colobinae). Compared with macaque monkeys (subfamily Cercopithecinae), colobines have lower sensitivities to PTC in behavioural and in vitro functional analyses. We identified four non-synonymous mutations in colobine TAS2R38 that are responsible for the decreased sensitivity of the TAS2R38 receptor to PTC observed in colobines compared with macaques. These results suggest that tolerance to bitterness in colobines evolved from an ancestor that was sensitive to bitterness as an adaptation to eating leaves.
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Su, Yuan, Hang Jie, Qing Zhu, Xiaoling Zhao, Yan Wang, Huadong Yin, Shailendra Kumar Mishra, and Diyan Li. "Effect of Bitter Compounds on the Expression of Bitter Taste Receptor T2R7 Downstream Signaling Effectors in cT2R7/pDisplay-Gα16/gust44/pcDNA3.1 (+) Cells." BioMed Research International 2019 (October 31, 2019): 1–12. http://dx.doi.org/10.1155/2019/6301915.
Full textAbstract:
Bitterness is an important taste sensation for chickens, which provides useful sensory information for acquisition and selection of diet, and warns them against ingestion of potentially harmful and noxious substances in nature. Bitter taste receptors (T2Rs) mediate the recognition of bitter compounds belonging to a family of proteins known as G-protein coupled receptors. The aim of this study was to identify and evaluate the expression of T2R7 in chicken tongue tissue and construct cT2R7-1 and cT2R7-2-expressing HEK-293T cells to access the expression of PLCβ2 and ITPR3 after exposure with different concentrations of the bitter compounds. Using real-time PCR, we show that the relative expression level of T2R7 mRNA in 5, 1, 0.1, and 10−3 mM of camphor and erythromycin solutions and 5 mM of chlorpheniramine maleate solutions was significantly higher than that in 50 mM KCL solutions. We confirmed that the bitter taste receptor T2R7 and downstream signaling effectors are sensitive to different concentrations of bitter compounds. Moreover, T2R7-1 (corresponding to the unique haplotype of the Tibetan chicken) had higher sensitivity to bitter compounds compared with that of T2R7-2 (corresponding to the unique haplotype of the Jiuyuan black-chicken). These results provide great significance of taste response on dietary intake to improve chicken feeding efficiency in poultry production and have certain reference value for future taste research in other bird species.
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Barragán, Rocio, Oscar Coltell, Olga Portolés, Eva Asensio, José Sorlí, Carolina Ortega-Azorín, José González, et al. "Bitter, Sweet, Salty, Sour and Umami Taste Perception Decreases with Age: Sex-Specific Analysis, Modulation by Genetic Variants and Taste-Preference Associations in 18 to 80 Year-Old Subjects." Nutrients 10, no. 10 (October 18, 2018): 1539. http://dx.doi.org/10.3390/nu10101539.
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There is growing interest in relating taste perception to diet and healthy aging. However, there is still limited information on the influence of age, sex and genetics on taste acuity as well as on the relationship between taste perception and taste preferences. We have analysed the influence of age on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a “total taste score”) and their modulation by sex and genetics in a relatively healthy population (men and women) aged 18–80 years (n = 1020 Caucasian European participants). Taste perception was determined by challenging subjects with solutions of the five basic tastes using standard prototypical tastants (6-n-propylthiouracil (PROP), NaCl, sucrose, monopotassium glutamate and citric acid) at 5 increasing concentrations (I to V). We also measured taste preferences and determined the polymorphisms of the genes taste 2 receptor member 38 (TAS2R38), taste 1 receptor member 2 (TAS2R38) and sodium channel epithelial 1 beta subunit (SCNN1B), as TAS2R38-rs713598, TAS1R2-rs35874116 and SCNN1B-rs239345 respectively. We found a statistically significant decrease in taste perception (“total taste score”) with increasing age for all the concentrations analysed. This association was stronger for the higher concentrations (p = 0.028; p = 0.012; p = 0.005; p = 4.20 × 10−5 and p = 1.48 × 10−7, for I to V in the multivariable-adjusted models). When we analysed taste qualities (using concentration V), the intensity rating of all the 5 tastes was diminished with age (p < 0.05 for all). This inverse association differed depending on the test quality, being higher for bitter (PROP) and sour. Women perceived taste significantly more intense than men (p = 1.4 × 10−8 for total taste score). However, there were differences depending on the taste, umami being the lowest (p = 0.069). There was a complex association between the ability to perceive a taste and the preference for the same. Significant associations were, nevertheless, found between a higher perception of sour taste and a higher preference for it in women. In contrast, the higher perception of sweet was significantly associated with a higher preference for bitter in both, men and women. The TAS2R38-rs713598 was strongly associated with bitter (PROP) taste (p = 1.38 × 10−50), having a significant interaction with sex (p = 0.030). The TAS1R2-rs35874116 was not significantly associated with sweet, whereas the SCNN1B-rs239345 was associated (p = 0.040) with salty taste. In conclusion, the inverse association between age and perceived taste intensity as well as the additional influence of sex and some genetic polymorphisms give rise to large inter-individual differences in taste perception and taste preferences that should be taken into account in future studies and for applications in precision nutrition for healthy aging.
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Di Pizio, Antonella, and Alessandro Nicoli. "In Silico Molecular Study of Tryptophan Bitterness." Molecules 25, no. 20 (October 11, 2020): 4623. http://dx.doi.org/10.3390/molecules25204623.
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Tryptophan is an essential amino acid, required for the production of serotonin. It is the most bitter amino acid and its bitterness was found to be mediated by the bitter taste receptor TAS2R4. Di-tryptophan has a different selectivity profile and was found to activate three bitter taste receptors, whereas tri-tryptophan activated five TAS2Rs. In this work, the selectivity/promiscuity profiles of the mono-to-tri-tryptophans were explored using molecular modeling simulations to provide new insights into the molecular recognition of the bitter tryptophan. Tryptophan epitopes were found in all five peptide-sensitive TAS2Rs and the best tryptophan epitope was identified and characterized at the core of the orthosteric binding site of TAS2R4.
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Conte, Caroline, Martin Ebeling, Anne Marcuz, Patrick Nef, and Pedro J. Andres-Barquin. "Evolutionary relationships of the Tas2r receptor gene families in mouse and human." Physiological Genomics 14, no. 1 (June 24, 2003): 73–82. http://dx.doi.org/10.1152/physiolgenomics.00060.2003.
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The early molecular events in the perception of bitter taste start with the binding of specific water-soluble molecules to G protein-coupled receptors (GPCRs) encoded by the Tas2r family of taste receptor genes. The identification of the complete TAS2R receptor family repertoire in mouse and a comparative study of the Tas2r gene families in mouse and human might help to better understand bitter taste perception. We have identified, cloned, and characterized 13 new mouse Tas2r sequences, 9 of which encode putative functional bitter taste receptors. The encoded proteins are between 293 and 333 amino acids long and share between 18% and 54% sequence identity with other mouse TAS2R proteins. Including the 13 sequences identified, the mouse Tas2r family contains ∼30% more genes and 60% fewer pseudogenes than the human TAS2R family. Sequence and phylogenetic analyses of the proteins encoded by all mouse and human Tas2r genes indicate that TAS2R proteins present a lower degree of sequence conservation in mouse than in human and suggest a classification in five groups that may reflect a specialization in their functional activity to detect bitter compounds. Tas2r genes are organized in clusters in both mouse and human genomes, and an analysis of these clusters and phylogenetic analyses indicates that the five TAS2R protein groups were present prior to the divergence of the primate and rodent lineages. However, differences in subsequent evolutionary processes, including local duplications, interchromosomal duplications, divergence, and deletions, gave rise to species-specific sequences and shaped the diversity of the current TAS2R receptor families during mouse and human evolution.
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Raka, Fitore, Sarah Farr, Jacalyn Kelly, Alexandra Stoianov, and Khosrow Adeli. "Metabolic control via nutrient-sensing mechanisms: role of taste receptors and the gut-brain neuroendocrine axis." American Journal of Physiology-Endocrinology and Metabolism 317, no. 4 (October 1, 2019): E559—E572. http://dx.doi.org/10.1152/ajpendo.00036.2019.
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Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well characterized and involve lingual taste receptors. These include heterodimers of G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli, the T2R family for sensing bitter stimuli, and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient-sensing mechanisms along the gastrointestinal tract. Glucose sensing is achieved by the T1R2-T1R3 heterodimer on enteroendocrine cells, which plays a role in triggering the secretion of incretin hormones for improved glycemic and lipemic control. Protein hydrolysates are detected by Ca2+-sensing receptor, the T1R1-T1R3 heterodimer, and G protein-coupled receptor 92/93 (GPR92/93), which leads to the release of the gut-derived satiety factor cholecystokinin. Furthermore, several GPCRs have been implicated in fatty acid sensing: GPR40 and GPR120 respond to medium- and long-chain fatty acids, GPR41 and GPR43 to short-chain fatty acids, and GPR119 to endogenous lipid derivatives. Aside from the recognition of fuel substrates, both the oral cavity and the gastrointestinal tract also possess T2R-mediated mechanisms of recognizing nonnutrients such as environmental contaminants, bacterial toxins, and secondary plant metabolites that evoke a bitter taste. These gastrointestinal sensing mechanisms result in the transmission of neuronal signals to the brain through the release of gastrointestinal hormones that act on vagal and enteric afferents to modulate the physiological response to nutrients, particularly satiety and energy homeostasis. Modulating these orally accessible nutrient-sensing pathways using particular foods, dietary supplements, or pharmaceutical compounds may have therapeutic potential for treating obesity and metabolic diseases.
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Chandrasekaran, Subhiksha, and Elvira Gonzalez de Mejia. "Effect of Germinated Chickpea Protein Hydrolysate on Markers of Type-2 Diabetes and Its Relationship to Bitter Taste Receptor Expression." Current Developments in Nutrition 6, Supplement_1 (June 2022): 274. http://dx.doi.org/10.1093/cdn/nzac053.015.
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Abstract Objectives To evaluate the effect of an optimized germinated chickpea protein hydrolysate (GCPH) on markers of type-2 diabetes such as dipeptidyl peptidase-IV (DPP-IV) inhibition, glucose uptake and expression of glucose transporters in enterocytes and their relationship to bitter taste receptor expression. Methods GCPH was characterized using LC-ESI-MS/MS. The bioactivity of the peptides and bitterness were characterized using the BioPep database. Predicted activation of bitter receptors was determined with BitterX. The energy of affinity was determined using molecular docking with DPP-IV, SGLT1, GLUT2, lipoprotein lipase (LPL) and fatty acid synthase (FAS). Glucose uptake was evaluated in Caco-2 cells and 3T3-L1 MBX adipocytes. The expression of glucose transporters SGLT1and GLUT2, and DPP-IV inhibition after GCPH treatment were also evaluated in Caco-2 cells. Lipid accumulation, triglycerol content, LPL and FAS activities were analyzed in 3T3-L1 MBX adipocytes. Results Three peptides, FDLPAL, GEAGR and VVFW were identified from legumin, all of which inhibited DPP-IV. Bitter fragments were found in several peptides and were predicted to activate bitter receptor hTAS2R14. FDLPAL was the most potent peptide inhibiting DPP-IV (−9.4 kcal/mol), SGLT1 (−9.3 kcal/mol) the enoyl-acyl carrier protein-reductase domain (−10.5 kcal/mol) and FAS β-ketoacyl reductase domain (−8.9 kcal/mol). VVFW was the most potent in inhibiting LPL (−6.6 kcal/mol) and GLUT2 (−11.2 kcal/mol). GEAGR was the most potent inhibitor of FAS thioesterase domain (−7.4 kcal/mol). GCPH inhibited DPP-IV (P < 0.05) in Caco-2 cells (IC50 2.1 mM) and glucose uptake at 1 mM (22%, P < 0.05) compared to untreated cells. GLUT2 expression was not different from a known inhibitor (phloretin, 100 μM, p > 0.05) at 2.5 mM. Bitter receptor TAS2R38 expression was suppressed with GCPH increasing concentrations up to 6.4-fold at 2.5 mM GCPH. Conclusions GCPH inhibited glucose uptake in enterocytes and GLUT2, DPP-IV and TAS2R38 in a dose-dependent manner. GCPH showed potential to be used as a functional ingredient in industrially processed foods. Funding Sources USDA\Pulse Crop Health Initiative.
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Kaufman, Adam C., Lauren Colquitt, Michael J. Ruckenstein, Douglas C. Bigelow, Steven J. Eliades, Guoxiang Xiong, Cailu Lin, Danielle R. Reed, and Noam A. Cohen. "Bitter Taste Receptors and Chronic Otitis Media." Otolaryngology–Head and Neck Surgery 165, no. 2 (January 12, 2021): 290–99. http://dx.doi.org/10.1177/0194599820984788.
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Objective To evaluate the presence of bitter taste receptors (T2Rs) in the middle ear and to examine their relationship with chronic ear infections. Study Design Cross-sectional study. Setting Tertiary care hospital. Methods This study enrolled 84 patients being evaluated for otologic surgery: 40 for chronic otitis media (COM) and 44 for other surgical procedures (controls). We collected a small piece of mucosa from 14 patients for mRNA analysis and from 23 patients for immunohistochemistry. A total of 55 patients underwent a double-blind taste test to gauge sensitivity to phenylthiocarbamide, denatonium, quinine, sucrose, and sodium chloride; 47 patients gave a salivary sample for single-nucleotide polymorphism analysis of rs1376251 ( TAS2R50) and rs1726866 ( TAS2R38). Results Bitter taste receptors were found in all samples, but the repertoire varied among patients. T2R50 was the most consistently identified receptor by mRNA analysis. Its rs1376251 allele was related to susceptibility to COM but not the expression pattern of T2R50. Ratings of bitterness intensity of phenylthiocarbamide, a ligand for T2R38, differed significantly between the COM and control groups. Conclusion T2Rs were found within the middle ear of every patient sampled; the rs1376251 allele of TAS2R50 appears to be related to chronic ear infections. These receptors are an intriguing target for future research and possible drug targeting.
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MIGUET, LAURENCE, ZIDING ZHANG, and MARTIN G. GRIGOROV. "Computational Studies of Ligand-Receptor Interactions in Bitter Taste Receptors." Journal of Receptors and Signal Transduction 26, no. 5-6 (January 2006): 611–30. http://dx.doi.org/10.1080/10799890600928210.
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