Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells

Ruiz-Avila, Luis; McLaughlin, Susan K.; Wildman, David E.; McKinnon, Peter J.; Robichon, Alain; Spickofsky, Nancy; Margolskee, Robert F.

doi:10.1038/376080a0

Cited by 195 publications

(164 citation statements)

References 29 publications

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“…Thus, their role as taste receptors is debatable. Recently, receptor-like activity stimulated by a bitter taste substance (denatonium) has been demonstrated, but not purified, from bovine lingual membranes (Ruiz-Avila et al, 1995). Our results with mGluR4 are the first to demonstrate a receptor by molecular cloning that is expressed in taste buds and not in surrounding epithelium, making it a plausible candidate for a taste receptor.…”

Section: Discussionmentioning

confidence: 63%

“…If mGluR4 is a taste receptor, its activation by dietary glutamate would presumably trigger a second messenger cascade that could regulate the transduction of other taste stimuli. Although several G-proteins, including gustducin and transducin, are localized in taste buds Finger et al, 1995;Ruiz-Avila et al, 1995), a functional linkage with mGluRs remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…al., 1984; Akabas et al, 1988;Avenet et al, 1988;Cummings et al, 1993) and biochemical (Striem et al, 1989;Hwang et al, 1990;Striem et al, 1991;Ruiz-Avila et al, 1995) evidence suggests that some stimuli, such as saccharin, sucrose, and denatonium (an intensely bitter compound), also may be mediated via G-proteincoupled pathways. Receptors, similar to those in olfactory neurons, have been cloned from lingual epithelia but do not appear to be expressed in taste buds (Abe et al, 1993;Matsuoka et al, 1993).…”

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confidence: 99%

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The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

et al. 1996

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Receptor proteins for photoreception have been studied for several decades. More recently, putative receptors for olfaction have been isolated and characterized. In contrast, no receptors for taste have been identified yet by molecular cloning. This report describes experiments aimed at identifying a receptor responsible for the taste of monosodium glutamate (MSG). Using reverse transcriptase (IV)-PCR, we found that several ionotropic glutamate receptors are present in rat lingual tissues. However, these receptors also could be detected in lingual tissue devoid of taste buds. On the other hand, RT-PCR and RNase protection assays indicated that a G-protein-coupled metabotropic glutamate receptor, mGluR4, also is expressed in lingual tissues and is limited only to taste buds. In situ hybridization demonstrated that mGluR4 is detectable in 40-70% of vallate and foliate taste buds but not in surrounding nonsensory epithelium, confirming the localization of this metabotropic receptor to gustatory cells. Expression of mGluR4 in taste buds is higher in preweaning rats compared with adult rats. This may correspond to the known higher sensitivity to the taste of MSG in juvenile rodents. Finally, behavioral studies have indicated that MSG and L-2-amino-4-phosphonobutyrate (L-AP4), a ligand for mGluR4, elicit similar tastes in rats. We conclude that mGluR4 may be a chemosensory receptor responsible, in part, for the taste of MSG.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

et al. 1996

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“…The ␣ subunit of transducins 1 (G␣ t-1 ) and 2 (G␣ t-2 ), originally thought to be expressed only in photoreceptor cells of the retina, are also present in vertebrate taste cells where they are implicated in intracellular taste signal transduction (7,8). Here, we used RT-PCR and immunohistochemistry to determine whether the transducins also are expressed in the GI mucosa.…”

Section: Expression Of Gustducin (G␣gust) and Transducin (G␣t-2) In Rmentioning

confidence: 99%

“…These putative taste receptors, which belong to the guanine nucleotide-binding regulatory protein (G protein)-coupled receptor superfamily characterized by seven putative transmembrane domains, are distantly related to V1R vomeronasal receptors and opsins (5). Genetic and biochemical evidence indicate that specific G␣ subunits, gustducin (G␣ gust ) and transducin (G␣ t ), mediate bitter and sweet gustatory signals in the taste buds of the lingual epithelium (7)(8)(9)(10)(11).…”

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confidence: 99%

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

Rozengurt

Yang

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

433

364

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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 ␣ subunits of G proteins implicated in intracellular taste signal transduction, namely G␣gust, and G␣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.stomach ͉ intestine ͉ gustducin ͉ transducin T he gustatory system has been selected during evolution to detect nutritive and beneficial compounds as well as harmful or toxic substances (1, 2). In particular, bitter taste has evolved as a central warning signal against the ingestion of potentially toxic substances (3). Recently, a large family of bitter taste receptors (T2Rs) expressed in specialized neuroepithelial taste receptor cells organized within taste buds in the tongue has been identified in humans and rodents (4-6). These putative taste receptors, which belong to the guanine nucleotide-binding regulatory protein (G protein)-coupled receptor superfamily characterized by seven putative transmembrane domains, are distantly related to V1R vomeronasal receptors and opsins (5). Genetic and biochemical evidence indicate that specific G␣ subunits, gustducin (G␣ gust ) and transducin (G␣ t ), mediate bitter and sweet gustatory signals in the taste buds of the lingual epithelium (7-11).Outside the tongue, expression of G␣ gust also has been localized to gastric (12) and pancreatic (13) cells, suggesting that a taste-sensing mechanism also may exist in the gastrointestinal (GI) tract. However, not all cells that express G␣ gust also coexpress members of the T2R family of receptors (5). For example, most G␣ gust -positive taste receptor cells in the lingual fungiform papillae are T2R-negative, implying that G␣ gust also could mediate signaling through other receptors (9). To establish that the gastric an...

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Light and dark cells of rat vallate taste buds are morphologically distinct cell types

1997

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Cells of mammalian taste buds have been classified into morphological types based on ultrastructural criteria, but investigators have disagreed as to whether these are distinct cell types or the extremes of a continuum. To address this issue, we examined taste buds from rat vallate papillae that had been sectioned transversely, rather than longitudinally, to their longest axis. In these transverse sections, dark (Type I) and light (Type II) cells were easily distinguished by their relative electron density, shape and topological relationships. Cells with electron-lucent cytoplasm (light cells) were circular or oval in outline, while those with electron-dense cytoplasm (dark cells) had an irregular outline with sheetlike cytoplasmic projections that separated adjacent light cells. A hierarchical cluster analysis of 314 cells across five morphological parameters (cell shape and area, and nuclear ellipticity, electron density and invagination) revealed two distinct groups of cells, which largely corresponded to the dark and light cells identified visually. These cells were not continuously distributed within a principal components factor solution. Differences in the means for dark and light cells were highly significant for each morphological parameter, but within either cell type, changes in one parameter correlated little with changes in any other. These analyses all failed to reveal cells with a consistent set of intermediate characteristics, suggesting that dark and light cells of rat vallate taste buds are distinct cell types rather than extremes of a continuum. Sections of taste buds were stained with antibodies to several carbohydrates, then observed by indirect immunofluorescence. Optical sections taken with a confocal laser-scanning microscope showed that the Lewis antigen was present only on spindle-shaped cells with circular or oval outlines and lacking transverse projections; these characteristic shapes matched those of light cells seen by electron microscopy. The H blood group antigen and the 2B8 epitope appeared at most cell-cell interfaces in the bud and are present on dark cells and possibly on some light cells. These findings relate molecular markers to morphological phenotypes and should facilitate future studies of taste cell turnover, development and regeneration.

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Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells

Cited by 195 publications

References 29 publications

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

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

Light and dark cells of rat vallate taste buds are morphologically distinct cell types

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