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TAS2R38 Predisposition to Bitter Taste Associated with Differential Changes in Vegetable Intake in Response to a Community-Based Dietary Intervention.

Although vegetable consumption associates with decreased risk for a variety of diseases, few Americans meet dietary recommendations for vegetable intake. TAS2R38 encodes a taste receptor that confers bitter taste sensing from chemicals found in some vegetables. Common polymorphisms in TAS2R38 lead to coding substitutions that alter receptor function and result in the loss of bitter taste perception. Our study examined whether bitter taste perception TAS2R38 diplotypes associated with vegetable consumption in participants enrolled in either an enhanced or a minimal nutrition counseling intervention. DNA was isolated from the peripheral blood cells of study participants (N = 497) and analyzed for polymorphisms. Vegetable consumption was determined using the Block Fruit and Vegetable screener. We tested for differences in the frequency of vegetable consumption between intervention and genotype groups over time using mixed effects models. Baseline vegetable consumption frequency did not associate with bitter taste diplotypes (P = 0.937), however after six months of the intervention, we observed an interaction between bitter taste diplotypes and time (P = 0.046). Participants in the enhanced intervention increased their vegetable consumption frequency (P = 0.020) and within this intervention group, the bitter non-tasters and intermediate-bitter tasters had the largest increase in vegetable consumption. In contrast, in the minimal intervention group, the bitter tasting participants reported a decrease in vegetable consumption. Bitter-non tasters and intermediate-bitter tasters increased vegetable consumption in either intervention more than those who perceive bitterness. Future precision medicine applications could consider genetic variation in bitter taste perception genes when designing dietary interventions.

Adolescent↗

IP(3) receptor type 3 and PLCbeta2 are co-expressed with taste receptors T1R and T2R in rat taste bud cells.

The Ca(2+) signaling cascade has been reported to be activated by many tastants in vertebrate taste systems. Recently we have shown that G(i2) and phospholipase Cbeta2 (PLCbeta2) are co-expressed in a subset of taste bud cells and are possibly involved in Ca(2+) triggering of taste signaling in rats. We report here that, as a component downstream of PLCbeta2, the type 3 isoform of the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R3) is specifically expressed in the same cells as PLCbeta2 in rat taste buds. We also show that cells expressing rT2R9, a probable cycloheximide receptor, are included among PLCbeta2- and IP(3)R3-positive cells, as in the case of rT1R2, a different type of taste receptor. Our findings indicate that PLCbeta2 and IP(3)R3 co-localize together with G(i2) as downstream components of two different types of taste receptors, T1R and T2R, in taste bud cells.

Animals↗

Dietary soybean or seaweed (Kappaphycus sp.) modulates taste-related gene (tas1r1 and tas1r2.2) expression in Nile tilapia (Oreochromis niloticus).

Taste perception plays a central role in fish feeding behaviour by influencing feed recognition, intake, and nutrient sensing. As aquaculture increasingly adopts plant-based ingredients to replace fishmeal, understanding how these diets affect gustatory mechanisms is critical. This study evaluated TAS-family taste receptor genes in Nile tilapia (Oreochromis niloticus) fed nutritionally formulated diets containing fishmeal (TFM), soybean meal (TSB), red seaweed (Kappaphycus sp., TSW), alongside a natural meal (TNM) reference. Fish were reared for 62 days under controlled conditions, after which growth performance was evaluated, and tongue transcriptomes were analysed using RNA sequencing to identify diet-associated gene expression changes. Candidate TAS1R and TAS2R receptors were identified through conserved domain screening and phylogenetic validation, and differential expression analysis was performed using DESeq2. Growth performance did not differ significantly among diets, although the soybean group showed the highest weight gain. Under the conditions of this study, most taste-related genes remained transcriptionally stable across formulated diets, indicating limited responsiveness of the gustatory system to ingredient substitution. Transcriptional differences were mainly observed in comparisons involving the TNM (TSB vs TNM and TSW vs TNM), where tas1r1 was upregulated, suggesting altered amino acid sensing relative to the non-formulated diet. Among formulated diets, tas1r2.2 was upregulated in the TSW vs TFM comparison, indicating potential modulation of carbohydrate-related taste pathways associated with seaweed inclusion. No reliable TAS2R transcripts were detected, likely due to low expression or tissue-specific distribution. Overall, taste receptor expression in Nile tilapia appears resilient to dietary variation, with selective modulation of TAS1R genes providing molecular insight into chemosensory adaptation to sustainable feed ingredients.

Animals↗

Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells.

Although a role for the gastric and intestinal mucosa in molecular sensing has been known for decades, the initial molecular recognition events that sense the chemical composition of the luminal contents has remained elusive. Here we identified putative taste receptor gene transcripts in the gastrointestinal tract. Our results, using reverse transcriptase-PCR, demonstrate the presence of transcripts corresponding to multiple members of the T2R family of bitter taste receptors in the antral and fundic gastric mucosa as well as in the lining of the duodenum. In addition, cDNA clones of T2R receptors were detected in a rat gastric endocrine cell cDNA library, suggesting that these receptors are expressed, at least partly, in enteroendocrine cells. Accordingly, expression of multiple T2R receptors also was found in STC-1 cells, an enteroendocrine cell line. The expression of alpha subunits of G proteins implicated in intracellular taste signal transduction, namely Galpha(gust), and Galpha(t)-(2), also was demonstrated in the gastrointestinal mucosa as well as in STC-1 cells, as revealed by reverse transcriptase-PCR and DNA sequencing, immunohistochemistry, and Western blotting. Furthermore, addition of compounds widely used in bitter taste signaling (e.g., denatonium, phenylthiocarbamide, 6-n-propil-2-thiouracil, and cycloheximide) to STC-1 cells promoted a rapid increase in intracellular Ca(2+) concentration. These results demonstrate the expression of bitter taste receptors of the T2R family in the mouse and rat gastrointestinal tract.

Animals↗

T2Rs function as bitter taste receptors.

Bitter taste perception provides animals with critical protection against ingestion of poisonous compounds. In the accompanying paper, we report the characterization of a large family of putative mammalian taste receptors (T2Rs). Here we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains deficient in their ability to detect cycloheximide have amino acid substitutions in the mT2R-5 gene; these changes render the receptor significantly less responsive to cycloheximide. We also expressed mT2R-5 in insect cells and demonstrate specific tastant-dependent activation of gustducin, a G protein implicated in bitter signaling. Since a single taste receptor cell expresses a large repertoire of T2Rs, these findings provide a plausible explanation for the uniform bitter taste that is evoked by many structurally unrelated toxic compounds.

Afferent Pathways↗

Identification of coding single-nucleotide polymorphisms in human taste receptor genes involving bitter tasting.

T2Rs comprise a G-protein-coupled receptor superfamily that contains functionally defined bitter taste receptors. Here we report the tissue expressions and coding single-nucleotide polymorphisms (cSNPs) in human T2R genes (hT2R3, hT2R4, and hT2R5) on chromosome 7q31. We first demonstrated that hT2R3, hT2R4, and hT2R5 are actually expressed in the circumvallate papillae of the human tongue by reverse transcription-polymerase chain reaction (RT-PCR). We identified six cSNPs within the T2R receptor genes. The hT2R4 and hT2R5 contained four and one cSNPs that cause missense mutations, respectively, while hT2R3 included one silent nucleotide mutation. However, we could not find any nonsense mutations that resulted in a frameshift or a premature stop codon within the open reading frames. Genotype frequencies of each cSNP were in Hardy-Weinberg equilibrium. The identification of nucleotide diversity and amino acid polymorphisms in human T2R receptors could help clarify individual differences in the acceptability and sensitivity to bitter compounds.

Base Sequence↗

Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity.

Taste represents a major form of sensory input in the animal kingdom. In mammals, taste perception begins with the recognition of tastant molecules by unknown membrane receptors localized on the apical surface of receptor cells of the tongue and palate epithelium. We report the cloning and characterization of two novel seven-transmembrane domain proteins expressed in topographically distinct subpopulations of taste receptor cells and taste buds. These proteins are specifically localized to the taste pore and are members of a new group of G protein-coupled receptors distantly related to putative mammalian pheromone receptors. We propose that these genes encode taste receptors.

Animals↗

A novel family of mammalian taste receptors.

In mammals, taste perception is a major mode of sensory input. We have identified a novel family of 40-80 human and rodent G protein-coupled receptors expressed in subsets of taste receptor cells of the tongue and palate epithelia. These candidate taste receptors (T2Rs) are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. Notably, a single taste receptor cell expresses a large repertoire of T2Rs, suggesting that each cell may be capable of recognizing multiple tastants. T2Rs are exclusively expressed in taste receptor cells that contain the G protein alpha subunit gustducin, implying that they function as gustducin-linked receptors. In the accompanying paper, we demonstrate that T2Rs couple to gustducin in vitro, and respond to bitter tastants in a functional expression assay.

Animals↗

Taste processing: whetting our appetites.

Two G-protein-coupled receptors have been identified that are present in the apical membranes of rat and mouse taste cells and differentially distributed across the tongue and palate. They are strong candidates for being taste receptors and their discovery has provided new tools for research into gustatory processing.

Animals↗

Membrane properties and cell ultrastructure of taste receptor cells in Necturus lingual slices.

1. Whole cell patch-clamp recordings and electron micrographs were obtained from cells in Necturus taste buds in lingual slices to study their membrane properties and to correlate these properties with cell ultrastructure. 2. Two different populations of taste receptor cells could be identified: one type possessed voltage-gated Na+ and K+ (noninactivating) currents (group 1 cells); the other type possessed only K+ (inactivating) currents (group 2 cells). 3. The zero-current ("resting") potential (Vo) and whole cell resistance (Ro) of these two types of taste cells differed significantly. For group 1 cells, on average, Vo = -75 mV and Ro = 24.6 G omega, and for group 2 cells, Vo = -49 mV and Ro = 48.9 G omega. The difference in Ro was not explained completely by differences in cell sizes, suggesting that intrinsic membrane properties differed between the populations. 4. Cells injected with biocytin were the electron microscope after tissues were reacted with majority (14 of 16) of cells with voltage-gated Na+ and K+ currents (group 1 cells) were characterized by abundant rough endoplasmic reticulum and dense granular packets in the apical process. These are features of dark cells. All the cells that only possessed K+ currents (group 2 cells) were characterize by well-developed smooth endoplasmic reticulum and an absence granular packets. These features characterize light cells. 5. These findings indicate that there is a good, although not exact, correlation between electrophysiological properties and cell morphotype in Necturus taste bud cells. All dark cells possessed Na+ and K+ currents and thus would be expected to be capable of generating action potentials. Most light cells only possessed outward K+ currents and thus would be incapable of generating action potentials.

Animals↗

Intercellular signaling in Necturus taste buds: chemical excitation of receptor cells elicits responses in basal cells.

1. Taste cells in intact taste buds in slices of Necturus lingual epithelium were impaled with microelectrodes for intracellular recording. Two types of cells were investigated: taste receptor cells and basal cells. 2. Impaling cells in the apical end of taste buds resulted in intracellular records from taste receptor cells. Applying short pulses (100- to 200-ms duration) of 140 mM KCl solution to the apical pore elicited receptor potentials in the taste receptor cells. 3. Impaling cells in the base of the taste bud resulted in intracellular records from taste receptor cells and basal cells. KCl applied to the taste pore elicited responses in the basal region that varied greatly in both magnitude and time of onset. The latency of these responses (time of onset compared with the onset of the receptor potential) ranged from 0 to hundreds of milliseconds. 4. Impaled cells were identified by injecting Lucifer yellow after recording KCl responses for 21 cells. KCl responses recorded from identified basal cells all had latencies of greater than 75 ms. KCl responses from identified receptor cells all had latencies of less than 75 ms. 5. One explanation for the long latency of KCl responses recorded in basal cells is that the responses represent postsynaptic potentials. In agreement with this interpretation, long-latency responses, but not short-latency responses, were reversibly reduced by the Ca antagonist Cd (1 mM, 10- to 20-min bath exposure). 6. Long-latency responses also differed from short-latency responses in their voltage dependence. Short-latency responses had the same voltage dependence as apically recorded receptor potentials, increasing with hyperpolarization from resting potential with an extrapolated reversal potential near 0 mV. Long-latency responses were much less dependent on voltage in this range. 7. We measured the spread of exogenously applied KCl with potassium-sensitive electrodes. Long-latency responses were not generated by diffusion of applied KCl to the basal region of the taste bud. A small transient increase in extracellular potassium occurred at the base of the taste bud after chemostimulation at the apical pore. This increase was due to depolarization-evoked release of potassium from taste cells and did not cause the long-latency responses in basal cells. 8. We conclude that short-latency (less than 75 ms) responses recorded from cells situated in the bases of taste buds are electrotonically conducted receptor potentials generated at the apical region. Long-latency (greater than 75 ms) responses are consistent with recording postsynaptic responses in basal cells.

Animals↗

Differential expression of carbohydrate blood-group antigens on rat taste-bud cells: relation to the functional marker alpha-gustducin.

An afferent nerve fiber supplying a taste bud receives input from several taste receptor cells, yet is predominantly responsive to one of the classic taste qualities (salt, acid, sweet, or bitter). This specificity requires recognition between taste receptor cells and nerve fibers that may be mediated by surface markers correlating with function. In an effort to identify potential markers, we used immunofluorescence and confocal microscopy to examine expression of the oligosaccharide blood-group antigens Lewis(b), A, and H type 2 in taste buds of the rat oral cavity. We compared the distributions of these antigens with that of alpha-gustducin, a G-protein subunit implicated in responses to sweet- and bitter-tasting substances. The A and Lewis(b) antigens were present only on spindle-shaped cells whose apical processes reached the taste pore. These antigens were not present on epithelial cells surrounding taste buds, and Lewis(b) was not found elsewhere in the digestive tract. Lewis(b) and A were not removed by lipid extraction, suggesting that they are present on glycoproteins rather than glycolipids. All Lewis(b)-positive cells expressed alpha-gustducin, but only a fraction of alpha-gustducin-positive cells expressed Lewis(b). The fraction of taste-bud cells expressing Lewis(b) decreased in the order: vallate papillae > foliate papillae > nasoincisor duct. The epiglottis had almost no taste-bud cells that expressed Lewis(b). The A antigen appeared on taste-bud cells that also expressed alpha-gustducin in the order: foliate and vallate papillae > nasoincisor duct and epiglottis > fungiform papillae. In addition, the A antigen was present on many cells that lacked alpha-gustducin in foliate and vallate papillae. In vallate papillae, cells expressed either A or Lewis(b), but not both. Lewis(b) appears to be restricted to differentiated light cells that also express alpha-gustducin and may be involved in intercellular interactions of these cells.

Animals↗

What's so special about special visceral?

The brainstem is classically divided into functional columns including special and general subdivisions for somatic and visceral components. The term 'special visceral motor' is applied to branchiomotor nuclei, while 'special visceral sensory' refers to nuclei devoted to incoming gustatory and olfactory senses. The use of the term 'special visceral motor' is questioned in that the branchiomotor neurons function more like general somatic than general visceral motoneurons. The designation of taste and smell as 'special visceral sensory' systems seems inconsistent on several bases. First, taste and smell are not homologous systems: (1) the receptors are grossly dissimilar in morphology and relationship to other elements of the nervous system; (2) the two systems mediate very different behaviors and respond to different types of chemical stimuli, and (3) chemosensory systems are not 'special' (i.e. limited to cranial nerves) in that solitary chemoreceptor cells, which are distributed across the body surface, can be innervated by spinal or cranial nerves. Finally, taste is considered 'special' because it involves specialized chemosensory end organs; the visceral nerves also provide innervation to other specialized chemoreceptors (e.g. carotid body) which are considered part of the general visceral sensory system. Thus the term 'special visceral sensory' appears without solid foundation when applied to gustatory systems in contradistinction to nongustatory branchial and thoracic interoceptive systems. A reformulation of the functional columns of the brainstem is suggested in which six columns can be identified: (1) somatic motor; (2) branchial motor; (3) visceral motor; (4) visceral sensory; (5) somatic sensory, and (6) hair cell (dorsolateral placode) sensory.

Animals↗

Co-expression of calcium signaling components in vertebrate taste bud cells.

In order to investigate the molecular mechanism of calcium signaling pathways common to the vertebrate gustatory systems, we have analyzed the expression of their molecular components. We first identified a phospholipase C (PLC) beta subtype expressed in the taste buds of pond loach (Misgurnus anguillicaudatus), designated DPLCbeta2, which is closely related to mammalian PLCbeta2 shown recently to be expressed in rat taste buds. The taste bud-specific expression of PLCbeta2 in a fish species as well as rat strongly suggests that PLCbeta2 mediates the tastant-induced second messenger response in taste buds, which is common to vertebrates. Next, we examined the correlation of gene expression of the candidate components leading to PLCbeta2 activation in rat circumvallate papillae, including G proteins, G(i2) and gustducin, and a G protein-coupled receptor, TR2. As a result, it was shown that the mRNAs for PLCbeta2 and G(i2) co-exist in the same cells, and PLCbeta2- and G(i2)-positive cells include both gustducin-positive cells and TR2-positive cells. However, no correlation was found between the expressions of TR2 and gustducin as reported previously. Our results thus indicate that a taste transduction pathway comprising TR2, G(i2) and PLCbeta2 occurs in a subset of taste cells.

Animals↗

Gustative sensitivity to glucose improvement in diabetics after sulphonylurea.

Sensitivity of the gustatory receptor to glucose has been studied in 20 diabetic patients given tolbutamid and glibenclamid as treatment or examined in the tolbutamid tolerance test (TTT). Tolbutamid and glibenclamid treatment significantly improves the diabetic taste for glucose, both for detection threshold (DT) (p less than 0.01) and recognition threshold (RT) (p less than 0.001). Also in TTT there is a significant improvement of taste reception: DT falls at 2 h (p less than 0.05), RT falls more slowly at 3 h (p less than 0.05). There is no direct correlation between perception for sweet and glycemia and insulinemia increase in TTT. Our results suggest that glucose receptivity is dependent on a receptor glucose-insulin complex, and tolbutamid (and glibenclamid) besides its capacity to stimulate insulin secretion has even a peripheral action, at this receptor level.

Adolescent↗