PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Taste Receptors, Type 2”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2005

Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence.

A coding single-nucleotide polymorphism (cSNP), K172N, in hTAS2R16, a gene encoding a taste receptor for bitter beta -glucopyranosides, shows significant association with alcohol dependence (P = .00018). This gene is located on chromosome 7q in a region reported elsewhere to exhibit linkage with alcohol dependence. The SNP is located in the putative ligand-binding domain and is associated with an increased sensitivity to many bitter beta -glucopyranosides in the presence of the N172 allele. Individuals with the ancestral allele K172 are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is uncommon in European Americans (minor-allele frequency [MAF] 0.6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population.

Black or African American↗
PubMed2003

Taste sensitivities to PROP and PTC vary independently in mice.

Mammals use common mechanisms to detect, transduce and process taste stimulus information. For example, they share families of receptors that respond to amino acids, and sweet- and bitter-tasting stimuli. Nonetheless, it also clear that different species exhibit unique taste sensitivities that may reflect specific genetic variations. In humans, sensitivities to the chemically similar, bitter-tasting compounds 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC) are heritable and strongly correlated, suggesting a common genetic basis. However, it is unknown whether PROP and PTC taste sensitivities are similarly correlated in mice. Here we report that PROP and PTC taste sensitivities vary independently between two inbred strains of mice. In brief-access taste tests C3HeB/FeJ (C3) and SWR/J (SW) mice possess similar taste sensitivity to PTC, while SW mice are significantly more sensitive to PROP than are C3 mice. In two-bottle preference tests, however, SW mice display greater aversion to both compounds. This discrepancy may be explained by the observation that SW mice consumed taste solutions at a greater rate during the intake test than did C3 mice. Therefore, PTC avoidance is correlated with the amount of PTC consumed in the intake tests rather than the concentration of PTC tested. These findings suggest that post-ingestive factors play a significant role in PTC avoidance during intake tests and highlight an important advantage of brief-access tests over intake tests in resolving the gustatory and post-ingestive contributions to taste-related behaviors. Most strikingly, these results demonstrate that in mice, unlike in humans, PTC and PROP taste sensitivities vary independently, thereby suggesting a subtle functional diversity of bitter-taste mechanisms across mammalian species.

Animal Feed↗
PubMed2004

Identification of ligands for two human bitter T2R receptors.

Earlier, a family of G protein-coupled receptors, termed T2Rs, was identified in the rodent and human genomes through data mining. It was suggested that these receptors mediate bitter taste perception. Analysis of the human genome revealed that the hT2R family is composed of 25 members. However, bitter ligands have been identified for only three human receptors so far. Here we report identification of two novel ligand-receptor pairs. hT2R61 is activated by 6-nitrosaccharin, a bitter derivative of saccharin. hT2R44 is activated by denatonium and 6-nitrosaccharin. Activation profiles for these receptors correlate with psychophysical data determined for the bitter compounds in human studies. Functional analysis of hT2R chimeras allowed us to identify residues in extracellular loops critical for receptor activation by ligands. The discovery of two novel bitter ligand-receptor pairs provides additional support for the hypothesis that hT2Rs mediate a bitter taste response in humans.

Amino Acid Sequence↗
PubMed2004

Bitter taste study in a sardinian genetic isolate supports the association of phenylthiocarbamide sensitivity to the TAS2R38 bitter receptor gene.

Recently, a major locus on chromosome 7q was found in association with the taste sensitivity to phenylthiocarbamide (PTC) in humans. This region contains the TAS2R38 gene that encodes a member of the TAS2R bitter taste receptor family. Three SNPs within this gene demonstrated a strong association with taster status in Utah families and in an additional sample of 85 unrelated individuals. We studied a small isolated village in eastern Sardinia and carried out a genome-wide scan to map the genetic basis of PTC perception in this population. We performed both qualitative and quantitative PTC-taste linkage analysis. Qualitative analysis was carried out by defining a cut-off from the bimodal distribution of the trait and classifying subjects as tasters and non-tasters (75 and 25%, respectively). Linkage analysis on 131 subjects belonging to a unique large multi-generation pedigree comprising 239 subjects confirmed significant evidence for linkage at 7q35 also in our population. Haplotype analyses of the three SNPs inside the PTC gene allowed us to identify only two haplotypes that were associated with the non-taster phenotype (80% AVI homozygous) and to taster phenotype (40% PAV homozygous and 56% PAV/AVI heterozygous). Sex, age and haplotype effect explained 77.2 % of the total variance in PTC sensitivity.

Humans↗
PubMed2003

Adaptive diversification of bitter taste receptor genes in Mammalian evolution.

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.

Amino Acid Sequence↗
PubMed2004

Evolution of bitter taste receptors in humans and apes.

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.

Animals↗
PubMed2005

Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes.

Taste reception is fundamental to diet selection in many animals. The genetic basis underlying the evolution and diversity of taste reception, however, is not well understood. Recent discoveries of T1R sweet/umami receptor genes and T2R bitter receptor genes in humans and mice provided an opportunity to address this question. Here, we report the identification of 20 putatively functional T1R genes and 167 T2R genes from the genome sequences of nine vertebrates, including three fishes, one amphibian, one bird, and four mammals. Our comparative genomic analysis shows that orthologous T1R sequences are relatively conserved in evolution and that the T1R gene repertoire remains virtually constant in size across most vertebrates, except for the loss of the T1R2 sweet receptor gene in the sweet-insensitive chicken and the absence of all T1R genes in the tongueless western clawed frog. In contrast, orthologous T2R sequences are more variable, and the T2R repertoire diverges tremendously among species, from only three functional genes in the chicken to 49 in the frog. These evolutionary patterns suggest the relative constancy in the number and type of sweet and umami tastants encountered by various vertebrates or low binding specificities of T1Rs but a large variation in the number and type of bitter compounds detected by different species. Although the rate of gene duplication is much lower in T1Rs than in T2Rs, signals of positive selection are detected during the functional divergences of paralogous T1Rs, as was previously found among paralogous T2Rs. Thus, functional divergence and specialization of taste receptors generally occurred via adaptive evolution.

Animals↗
PubMed2004

Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake.

BACKGROUND: Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), chemically related compounds, are probes for genetic variation in bitter taste, although PROP is safer with less sulfurous odor. Threshold for PROP distinguishes nontasters (increased threshold) from tasters (lower threshold); perceived intensity subdivides tasters into medium tasters (PROP is bitter) and supertasters (PROP is very bitter). Compared with supertasters, nontasters have fewer taste papillae on the anterior tongue (fungiform papillae) and experience less negative (e.g., bitterness) and more positive (eg, sweetness) sensations from alcohol. We determined whether the TAS2R38 gene at 7q36 predicted PROP bitterness, alcohol sensation and use. METHODS: Healthy adults (53 women, 31 men; mean age 36 years)--primarily light and moderate drinkers--reported the bitterness of five PROP concentrations (0.032-3.2 mM) and intensity of 50% ethanol on the general Labeled Magnitude Scale. PROP threshold and density of fungiform papillae were also measured. Subjects had common TAS2R38 gene haplotypes [alanine-valine-isoleucine (AVI) and proline-alanine-valine (PAV)]. RESULTS: PROP bitterness varied significantly across genotypes with repeated measures ANOVA: 26 AVI/AVI homozygotes tasted less bitterness than either 37 PAV/AVI heterozygotes or 21 PAV/PAV homozygotes. The PAV/PAV group exceeded the PAV/AVI group for bitterness only for the top PROP concentrations. The elevated bitterness was musch less than if we defined the groups using psychophysical criteria. With multiple regression analyses, greater bitterness from 3.2 mM PROP was a significant predictor of greater ethanol intensity and less alcohol intake--effects separate from age and sex. Genotype was a significant predictor of alcohol intake, but not ethanol intensity. With ANOVA, AVI/AVI homozygotes reported higher alcohol use than either PAV/AVI heterozygotes or PAV/PAV homozygotes. When age effects were minimized, PROP bitterness explained more variance in alcohol intake than did the TAS2R38 genotype. CONCLUSIONS: These results support taste genetic effects on alcohol intake. PROP bitterness serves as a marker of these effects.

Adult↗
PubMed2005

Genetics of individual differences in bitter taste perception: lessons from the PTC gene.

The ability or inability to taste the compound phenylthiocarbamide (PTC) is a classic inherited trait in humans and has been the subject of genetic and anthropological studies for over 70 years. This trait has also been shown to correlate with a number of dietary preferences and thus may have important implications for human health. The recent identification of the gene that underlies this phenotype has produced several surprising findings. This gene is a member of the T2R family of bitter taste receptor genes. It exists in seven different allelic forms, although only two of these, designated the major taster and major non-taster forms, exist at high frequency outside sub-Saharan Africa. The non-taster allele resides on a small chromosomal region identical by descent, indicating that non-tasters are descended from an ancient founder individual, and consistent with an origin of the non-taster allele preceding the emergence of modern humans out of Africa. The two major forms differ from each other at three amino acid positions, and both alleles have been maintained at high frequency by balancing natural selection, suggesting that the non-taster allele serves some function. We hypothesize that this function is to serve as a receptor for another, as yet unidentified toxic bitter substance. At least some of the remaining five haplotypes appear to confer intermediate sensitivity to PTC, suggesting future detailed studies of the relationships between receptor structure and taste function.

Alleles↗
PubMed2004

RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells.

Abstract G-protein-mediated signalling processes are involved in sweet and bitter taste transduction. In particular, the G protein alpha-subunit gustducin has been implicated in these processes. One of the limiting factors for the time-course of cellular responses induced by tastants is therefore the intrinsic GTPase activity of alpha-gustducin, which determines the lifetime of the active G protein complex. In several signalling systems specific 'regulator of G protein signalling' (RGS) proteins accelerate the GTPase activity of G protein alpha-subunits. Using differential screening approaches, we have identified a novel RGS protein termed RGS21, which represents the smallest known member of this protein family. Reverse transcription polymerase chain reaction and in situ hybridization experiments demonstrated that RGS21 is expressed selectively in taste tissue where it is found in a subpopulation of sensory cells. Furthermore, it is coexpressed in individual taste cells with bitter and sweet transduction components including alpha-gustducin, phospholipase Cbeta2, T1R2/T1R3 sweet taste receptors and T2R bitter taste receptors. In vitro binding assays demonstrate that RGS21 binds alpha-gustducin in a conformation-dependent manner and has the potential to interact with the same Galpha subtypes as T1R receptors. These results suggest that RGS21 could play a regulatory role in bitter as well as sweet taste transduction processes.

Aluminum Compounds↗
PubMed2003

Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide.

The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibrium between single-nucleotide polymorphism (SNP) markers and PTC taste sensitivity in unrelated subjects. This region contains a single gene that encodes a member of the TAS2R bitter taste receptor family. We identified three coding SNPs giving rise to five haplotypes in this gene worldwide. These haplotypes completely explain the bimodal distribution of PTC taste sensitivity, thus accounting for the inheritance of the classically defined taste insensitivity and for 55 to 85% of the variance in PTC sensitivity. Distinct phenotypes were associated with specific haplotypes, which demonstrates that this gene has a direct influence on PTC taste sensitivity and that sequence variants at different sites interact with each other within the encoded gene product.

Alleles↗
PubMed2005

Genetic tracing shows segregation of taste neuronal circuitries for bitter and sweet.

The recent discovery of mammalian bitter, sweet, and umami taste receptors indicates how the different taste qualities are encoded at the periphery. However, taste representations in the brain remain elusive. We used a genetic approach to visualize the neuronal circuitries of bitter and sweet tastes in mice to gain insight into how taste recognition is accomplished in the brain. By selectively expressing a transsynaptic tracer in either bitter- or sweet and/or umami-responsive taste receptor cells, and by comparing the locations of the tracer-labeled neurons in the brain, our data revealed the potential neuronal bases that underlie discrimination of bitter versus sweet.

Animals↗