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Query: UMLS:C0235290 (bitter taste)
 1,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R/T2R family of taste receptor genes. TAS2R receptors are expressed at the surface of taste receptor cells and are coupled to G proteins and second messenger pathways. We have identified, cloned and characterized 11 new bitter taste receptor genes and four new pseudogenes that belong to the human TAS2R family. Their encoded proteins have between 298 and 333 amino acids and share between 23 and 86% identity with other human TAS2R proteins. Screening of a mono-chromosomal somatic cell hybrid panel to assign the identified bitter taste receptor genes to human chromosomes demonstrated that they are located in chromosomes 7 and 12. Including the 15 sequences identified, the human TAS2R family is composed of 28 full-length genes and 16 pseudogenes. Phylogenetic analyses suggest a classification of the TAS2R genes in five groups that may reflect a specialization in the detection of specific types of bitter chemicals.
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PMID:Identification and characterization of human taste receptor genes belonging to the TAS2R family. 1258 40

The diversity and evolution of bitter taste perception in mammals is not well understood. Recent discoveries of bitter taste receptor (T2R) genes provide an opportunity for a genetic approach to this question. We here report the identification of 10 and 30 putative T2R genes from the draft human and mouse genome sequences, respectively, in addition to the 23 and 6 previously known T2R genes from the two species. A phylogenetic analysis of the T2R genes suggests that they can be classified into three main groups, which are designated A, B, and C. Interestingly, while the one-to-one gene orthology between the human and mouse is common to group B and C genes, group A genes show a pattern of species- or lineage-specific duplication. It is possible that group B and C genes are necessary for detecting bitter tastants common to both humans and mice, whereas group A genes are used for species-specific bitter tastants. The analysis also reveals that phylogenetically closely related T2R genes are close in their chromosomal locations, demonstrating tandem gene duplication as the primary source of new T2Rs. For closely related paralogous genes, a rate of nonsynonymous nucleotide substitution significantly higher than the rate of synonymous substitution was observed in the extracellular regions of T2Rs, which are presumably involved in tastant-binding. This suggests the role of positive selection in the diversification of newly duplicated T2R genes. Because many natural poisonous substances are bitter, we conjecture that the mammalian T2R genes are under diversifying selection for the ability to recognize a diverse array of poisons that the organisms may encounter in exploring new habitats and diets.
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PMID:Adaptive diversification of bitter taste receptor genes in Mammalian evolution. 1267 30

Bitter taste perception is crucial for the survival of organisms because it enables them to avoid the ingestion of potentially harmful substances. Bitter taste receptors are encoded by a gene family that in humans has been shown to contain 25 putatively functional genes and 8 pseudogenes and in mouse 33 putatively functional genes and 3 pseudogenes. Lineage-specific expansions of bitter taste receptors have taken place in both mouse and human, but very little is known about the evolution of these receptors in primates. We report the analysis of the almost complete repertoires of bitter taste receptor genes in human, great apes, and two Old World monkeys. As a group, these genes seem to be under little selective constraint compared with olfactory receptors and other genes in the studied species. However, in contrast to the olfactory receptor gene repertoire, where humans have a higher proportion of pseudogenes than apes, there is no evidence that the rate of loss of bitter taste receptor genes varies among humans and apes.
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PMID:Evolution of bitter taste receptors in humans and apes. 1549 49

The sense of taste provides animals with valuable information about the nature and quality of food. Bitter taste detection functions as an important sensory input to warn against the ingestion of toxic and noxious substances. T2Rs are a family of approximately 30 highly divergent G-protein-coupled receptors (GPCRs) that are selectively expressed in the tongue and palate epithelium and are implicated in bitter taste sensing. Here we demonstrate, using a combination of genetic, behavioural and physiological studies, that T2R receptors are necessary and sufficient for the detection and perception of bitter compounds, and show that differences in T2Rs between species (human and mouse) can determine the selectivity of bitter taste responses. In addition, we show that mice engineered to express a bitter taste receptor in 'sweet cells' become strongly attracted to its cognate bitter tastants, whereas expression of the same receptor (or even a novel GPCR) in T2R-expressing cells resulted in mice that are averse to the respective compounds. Together these results illustrate the fundamental principle of bitter taste coding at the periphery: dedicated cells act as broadly tuned bitter sensors that are wired to mediate behavioural aversion.
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PMID:The receptors and coding logic for bitter taste. 1575 3

A family of approximately 30 TAS2R bitter taste receptors has been identified in mammals. Their genes evolved through adaptive diversification and are linked to chromosomal loci known to influence bitter taste in mice and humans. The agonists for various TAS2Rs have been identified and all of them were established as bitter tastants. TAS2Rs are broadly tuned to detect multiple bitter substances, explaining, in part, how mammals can recognize numerous bitter compounds with a limited set of receptors. The TAS2Rs are expressed in a subset of taste receptor cells, which are distinct from those mediating responses to other taste qualities. However, cells devoted to the detection of sweet, umami, and bitter stimuli share common signal transduction components. Transgenic expression of a human TAS2R in sweet or bitter taste receptor-expressing cells of mice induced either strong attraction or aversion to the receptor's cognate bitter tastant. Thus, dedicated taste receptor cells appear to function as broadly tuned detectors for bitter substances and are wired to elicit aversive behavior.
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PMID:Elucidation of mammalian bitter taste. 1603 95

The sense of bitter taste plays a critical role in how organisms avoid generally bitter toxic and harmful substances. Previous studies revealed that there were 25 intact bitter taste receptor (T2R) genes in humans and 34 in mice. However, because the recent chicken genome project reported only three T2R genes, it appears that extensive gene expansions occurred in the lineage leading to mammals or extensive gene contractions occurred in the lineage leading to birds. Here, I examined the T2R gene repertoire in placental mammals (dogs, Canis familiaris; and cows, Bos taurus), marsupials (opossums, Monodelphis domestica), amphibians (frogs, Xenopus tropicalis), and fishes (zebrafishes, Danio rerio; and pufferfishes, Takifugu rubripes) to investigate the birth-and-death process of T2R genes throughout vertebrate evolution. I show that (1) the first extensive gene expansions occurred before the divergence of mammals from reptiles/birds but after the divergence of amniotes (reptiles/birds/mammals) from amphibians, (2) subsequent gene expansions continuously took place in the ancestral mammalian lineage and the lineage leading to amphibians, as evidenced by the presence of 15, 18, 26, and 49 intact T2R genes in the dog, cow, opossum, and frog genome, respectively, and (3) contractions of the gene repertoire happened in the lineage leading to chickens. Thus, continuous gene expansions have shaped the T2R repertoire in mammals, but the contractions subsequent to the first round of expansions have made the chicken T2R repertoire narrow. These dramatic changes in the repertoire size might reflect the daily intake of foods from an external environment as a driving force of evolution.
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PMID:Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Lineage-specific expansions and contractions of the bitter taste receptor gene repertoire in vertebrates. 1648 89

The masking mechanisms of the bitter taste of propantheline bromide (PB) and oxyphenonium (OB) bromide by native and modified cyclodextrins, saccharides, surfactants, organic acids, nonionic and anionic polymers, and other compounds were investigated with ion selective electrodes. The intensity of the bitter taste for a mixed solution of cyclodextrin with PB or OB was quantitatively explained from the observed electromotive force with the following assumptions: the complex and the masking agent do not have any tastes and the bitter taste is independent of other tastes. Sodium dodecyl sulfate reduced the bitter taste remarkably, and this reduction was also explicable on the basis of the same mechanism. Sodium taurodeoxycholate enhanced the bitter taste, because of its strong bitterness, although it formed 1 : 1 complexes with PB and OB. The masking mechanism of saccharides was ascribed to overcoming the weak bitterness of the drug by the strong sweetness. Lambda-carrageenan suppressed the bitter taste remarkably. This suppression was ascribed to the binding of PB and OB to lambda-carrageenan, the effect of the solution viscosity on the bitter taste, and the covering of the bitter taste receptor by lambda-carrageenan. It was suggested that the moderate masking by other polymers was attributable to the effect of the solution viscosity or the receptor covering. Native and modified beta-cyclodextrins, sodium dodecyl sulfate, lambda-carrageenan, Tween 20, and sodium carboxymethyl cellulose are good masking agents for the bitter tastes of PB and OB. The drug ion selective electrode is a useful tool for understanding of the masking mechanism of the bitter taste, screening of masking agents, and estimation of appropriate concentrations of the masking agents.
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PMID:Masking mechanisms of bitter taste of drugs studied with ion selective electrodes. 1688 Jun 61

Phenylthiocarbamide tastes intensely bitter to some individuals, but others find it completely tasteless. Recently, it was suggested that phenylthiocarbamide elicits bitter taste by interacting with a human G protein-coupled receptor (hTAS2R38) encoded by the PTC gene. The phenylthiocarbamide nontaster trait was linked to three single nucleotide polymorphisms occurring in the PTC gene. Using the crystal structure of bovine rhodopsin as template, we generated the 3D structure of hTAS2R38 bitter taste receptor. We were able to map on the receptor structure the amino acids affected by the genetic polymorphisms and to propose molecular functions for two of them that explained the emergence of the nontaster trait. We used molecular docking simulations to find that phenylthiocarbamide exhibited a higher affinity for the target receptor than the structurally similar molecule 6-n-propylthiouracil, in line with recent experimental studies. A 3D model was constructed for the hTAS2R16 bitter taste receptor as well, by applying the same protocol. We found that the recently published experimental ligand binding affinity data for this receptor correlated well with the binding scores obtained from our molecular docking calculations.
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PMID:Computational studies of ligand-receptor interactions in bitter taste receptors. 1711 1

Sesquiterpene lactones are a major class of natural bitter compounds occurring in vegetables and culinary herbs as well as in aromatic and medicinal plants, where they often represent the main gustatory and pharmacologically active component. Investigations on sesquiterpene lactones have mainly focused on their bioactive potential rather than on their sensory properties. In the present study, we report about the stimulation of heterologously expressed human bitter taste receptors, hTAS2Rs, by the bitter sesquiterpene lactone herbolide D. A specific response to herbolide D was observed i.a. for hTAS2R46, a so far orphan bitter taste receptor without any known ligand. By further investigation of its agonist pattern, we characterized hTAS2R46 as a bitter receptor broadly tuned to sesquiterpene lactones and to clerodane and labdane diterpenoids as well as to the unrelated bitter substances strychnine and denatonium.
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PMID:Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. 1759 5

Human bitter taste is mediated by approximately 25 members of the human TAS2 receptor (hTAS2R) gene family. The hTAS2R genes are expressed in taste buds of gustatory papillae on the tongue surface. Because many naturally occurring bitter compounds are toxic, bitter taste receptors are believed to serve as warning sensors against the ingestion of toxic food compounds. An important question is whether bitter taste receptor cells are a homogeneous, broadly tuned population of cells, which uniformly express all bitter taste receptor genes, or not. Gene expression analyses in rodents demonstrated an essentially overlapping expression of TAS2R genes indicating a broad tuning, whereas functional in vivo analyses suggest a narrow tuning. The present study demonstrates the expression of all 25 human TAS2R genes in taste receptor cells of human circumvallate papillae. As shown by in situ hybridization experiments, the expression of hTAS2R genes differs in both the apparent level of expression and the number of taste receptor cells expressing these genes, suggesting a heterogeneous bitter taste receptor cell population. Differences in gene expression levels were verified by quantitative reverse transcription-PCR experiments for a subset of hTAS2R genes. Direct evidence for the heterogeneity of bitter taste receptor cells is provided by dual-labeling in situ hybridizations with selected pairs of hTAS2R gene-specific probes. Functional coexpression experiments in heterologous cells show competition among hTAS2Rs, indicating a possible biological reason for the observed expression pattern. From the data, we conclude that human bitter taste receptor cells are tuned to detect a limited subset of bitter stimuli.
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PMID:Gustatory expression pattern of the human TAS2R bitter receptor gene family reveals a heterogenous population of bitter responsive taste receptor cells. 1800 42


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