Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235290 (bitter taste)
 1,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rod and cone transducins are specific G proteins originally thought to be present only in photoreceptor cells of the vertebrate retina. Transducins convert light stimulation of photoreceptor opsins into activation of cyclic GMP phosphodiesterase (reviewed in refs. 5-7). A transducin-like G protein, gustducin, has been identified and cloned from rat taste cells. We report here that rod transducin is also present in vertebrate taste cells, where it specifically activates a phosphodiesterase isolated from taste tissue. Furthermore, the bitter compound denatonium in the presence of taste-cell membranes activates transducin but not Gi. A peptide that competitively inhibits rhodopsin activation of transducin also blocks taste-cell membrane activation of transducin, arguing for the involvement of a seven-transmembrane-helix G-protein-coupled receptor. These results suggest that rod transducin transduces bitter taste by coupling taste receptor(s) to taste-cell phosphodiesterase. Phosphodieterase-mediated degradation of cyclic nucleotides may lead to taste-cell depolarization through the recently identified cyclic-nucleotide-suppressible conductance.
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PMID:Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells. 759 26

In the vertebrate taste cell, heterotrimeric guanine nucleotide-binding proteins (G proteins) are involved in the transduction of both bitter and sweet taste stimulants. The bitter compound denatonium raises the intracellular Ca2+ concentration in rat taste cells, apparently via G protein-mediated increases in inositol trisphosphate. Sucrose causes a G protein-dependent generation of cAMP in rat taste bud membranes; elevation of cAMP levels leads to taste cell depolarization. To identify and characterize those proteins involved in the taste transduction process, we have cloned G protein alpha subunit (G alpha) cDNAs from rat taste cells. Using degenerate primers corresponding to conserved regions of G proteins, we used the polymerase chain reaction to amplify and clone taste cell G alpha cDNAs. Eight distinct G alpha cDNAs were isolated, cloned and sequenced from a taste cell library. Among these clones was alpha gustducin, a novel taste G alpha closely related to the transducins. In addition to alpha gustducin, we cloned rod and cone transducins from taste cells. This is the first identification of transducin expression outside photoreceptor cells. The primary sequence of alpha gustducin shows similarities to the transducins in the receptor interaction domain and the phosphodiesterase activation site. These sequence similarities suggest that gustducin and transducin regulate taste cell phosphodiesterase, probably in bitter taste transduction.
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PMID:Gustducin and transducin: a tale of two G proteins. 816 77

The mechanisms responsible for taste signal transductions are very complex. A key molecule, alpha-gustducin, a primarily taste-specific G protein alpha-subunit, was discovered in 1992 and was later found to be involved in both bitter and sweet taste transduction. A proposed mechanism for alpha-gustducin involves coupling specific cell-surface receptors with a cyclic nucleotide phosphodiesterase which would open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, and ultimately leading to release of neurotransmitter. Although "knock-out" animals deficient in the alpha-gustducin gene clearly demonstrate that gustducin is an essential molecule for tasting certain bitter and sweet compounds, the precise role of alpha-gustducin in bitter and sweet taste is presently unclear. Indeed, there are several other signaling mechanisms in sweet and bitter taste, apparently unrelated to alpha-gustducin, that increase cyclic AMP or inositol 1,4,5 trisphosphate. Thus, proposed models for alpha-gustducin and those found by other laboratories may be parallel and interdependent.
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PMID:Gustducin and its role in taste. 953 56

The two anomers of L-glucose pentaacetate were recently found to stimulate insulin release. The insulinotropic action of these esters cannot be attributed to the catabolism in islet cells of their glucidic or acetic moieties. The present review deals with an alternative hypothesis. It is proposed that L-glucose pentaacetate itself directly interacts with a yet unidentified receptor leading to plasma membrane depolarization, induction of electrical activity and increase in the cytosolic concentration of ionized Ca2+. This process displays analogies with the identification of bitter compounds by taste buds. Thus, beta-L-glucose pentaacetate indeed displays a bitter, but no sweet, taste. Purified islet B-cells contain the alpha-gustducin G-protein involved in the perception of bitter taste by taste buds. The pentaacetate ester of beta-L-glucose decreases 86Rb outflow from prelabelled islets, provokes bioelectrical activity in islet B-cells and may induce oscillations of cytosolic Ca2+ in these insulin-producing cells. The effects of beta-L-glucose pentaacetate upon glucagon and somatostatin secretion by the isolated perfused pancreas are also compatible with the present hypothesis. It is proposed that the L-glucose pentaacetate anomers could be used as novel insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus.
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PMID:The riddle of L-glucose pentaacetate insulinotropic action (review). 985 21

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.
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PMID:T2Rs function as bitter taste receptors. 1076 35

Current evidence points to the existence of multiple processes for bitter taste transduction. Previous work demonstrated involvement of the polyphosphoinositide system and an alpha-gustducin (Galpha(gust))-mediated stimulation of phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G protein gamma-subunit, Ggamma(13), colocalizes with Galpha(gust) and mediates the denatonium-stimulated production of inositol 1,4,5-trisphosphate (IP(3)). Using quench-flow techniques, we show here that the bitter stimuli, denatonium and strychnine, induce rapid (50-100 ms) and transient reductions in cAMP and cGMP and increases in IP(3) in murine taste tissue. This decrease of cyclic nucleotides is inhibited by Galpha(gust) antibodies, whereas the increase in IP(3) is not affected by antibodies to Galpha(gust). IP(3) production is inhibited by antibodies specific to phospholipase C-beta(2) (PLC-beta(2)), a PLC isoform known to be activated by Gbetagamma-subunits. Antibodies to PLC-beta(3) or to PLC-beta(4) were without effect. These data suggest a transduction mechanism for bitter taste involving the rapid and transient metabolism of dual second messenger systems, both mediated through a taste cell G protein, likely composed of Galpha(gust)/beta/gamma(13), with both systems being simultaneously activated in the same bitter-sensitive taste receptor cell.
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PMID:Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides. 1124 89

Previous studies in rat and mouse have shown that brief exposure to the bitter stimulus denatonium induces an increase in [Ca2+]i due to Ca2+ release from intracellular Ca2+ stores, rather than Ca2+ influx. We report here that prolonged exposure to denatonium induces sustained increases in [Ca2+]i that are dependent on Ca2+ influx. Similar results were obtained from taste cells of the mudpuppy, Necturus maculosus, as well as green fluorescent protein (GFP) tagged gustducin-expressing taste cells of transgenic mice. In a subset of mudpuppy taste cells, prolonged exposure to denatonium induced oscillatory Ca2+ responses. Depletion of Ca2+ stores by thapsigargin also induced Ca2+ influx, suggesting that Ca2+ store-operated channels (SOCs) are present in both mudpuppy taste cells and gustducin-expressing taste cells of mouse. Further, treatment with thapsigargin prevented subsequent responses to denatonium, suggesting that the SOCs were the source of the Ca2+ influx. These data suggest that SOCs may contribute to bitter taste transduction and to regulation of Ca2+ homeostasis in taste cells.
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PMID:Taste receptor cell responses to the bitter stimulus denatonium involve Ca2+ influx via store-operated channels. 1203 15

Bitter taste perception is a conserved chemical sense against the ingestion of poisonous substances in mammals. A multigene family of G-protein-coupled receptors, T2R (so-called TAS2R or TRB) receptors and a G-protein alpha subunit (Galpha), gustducin, are believed to be key molecules for its perception, but little is known about the molecular basis for its interaction. Here, we use a heterologous expression system to determine a specific domain of gustducin necessary for T2R coupling. Two chimeric Galpha16 proteins harboring 37 and 44 gustducin-specific sequences at their C termini (G16/gust37 and G16/gust44) responded to different T2R receptors with known ligands, but G16/gust 23, G16/gust11, and G16/gust5 did not. The former two chimeras contained a predicted beta6 sheet, an alpha5 helix, and an extreme C terminus of gustducin, and all the domains were indispensable to the expression of T2R activity. We also expressed G16 protein chimeras with the corresponding domain from other Galpha(i) proteins, cone-transducin (Galpha(t2)), Galpha(i2), and Galpha(z) (G16/t2, G16/i2, and G16/z). As a result, G16/t2 and G16/i2 produced specific responses of T2Rs, but G16/z did not. Because Galpha(t2) and Galpha(i2) are expressed in the taste receptor cells, these G-protein alpha(i) subunits may also be involved in bitter taste perception via T2R receptors. The present Galpha16-based chimeras could be useful tools to analyze the functions of many orphan G-protein-coupled taste receptors.
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PMID:Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells. 1291 72

Many bitter stimuli are believed to bind to specific G-protein-coupled membrane receptors on taste cells. Despite the compelling evidence for its pivotal role in bitter taste sensation, a direct involvement of the G-protein subunit alpha-gustducin in bitter taste transduction in taste cells has not been demonstrated in situ at the cellular level. We recorded activation of taste cells by bitter stimuli using Ca2+ imaging in lingual slices and examined alpha-gustducin immunoreactivity in the same cells. In mice vallate papillae, many, but not all, bitter-responsive cells expressed alpha-gustducin. In agreement with this correlation, the incidence of cells responding to bitter stimuli was reduced by 70% in mutant mice lacking alpha-gustducin. Nevertheless, some taste cells lacking alpha-gustducin responded to bitter stimuli, suggesting that other G-protein alpha subunits are involved. We found that the G-protein alpha subunit Galpha(i2) is present in most bitter-responsive cells and thus may also play a role in bitter taste transduction. The reduced behavioral sensitivity to bitter stimuli in alpha-gustducin knock-out mice thus appears to be the consequence of a reduced number of bitter-activated taste cells, as well as reduced sensitivity.
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PMID:Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli. 1458 25

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.
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PMID:RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells. 1506 50


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