Functional bitter taste receptors are expressed in brain cells

Singh, Nisha; Vrontakis, Maria; Parkinson, Fiona E.; Chelikani, Prashen

doi:10.1016/j.bbrc.2011.02.016

Cited by 153 publications

(134 citation statements)

References 30 publications

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“…Humans express approximately 25 TAS2 receptors, of which five TAS2Rs, TAS2Rs 7, 10, 14, 43, and 46, can be activated by caffeine (12). In addition to the mouth, TAS2Rs have also been identified in nongustatory tissues, including airway epithelia (13), brain (14), intestinal cells (15,16), and the gastric epithelia of rats and mice (17,18). Beyond their chemosensory function, extraoral TAS2Rs are involved in nonsensory processes to expel or neutralize toxins in the upper and lower airways as well as in the gastrointestinal tract (19).…”

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confidence: 99%

Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells

Liszt

Ley

Lieder

et al. 2017

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

186

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Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g., in the gastrointestinal tract, in which their functional role still needs to be clarified. We hypothesized that caffeine evokes effects on GAS by activation of oral and gastric TAS2Rs and demonstrate that caffeine, when administered encapsulated, stimulates GAS, whereas oral administration of a caffeine solution delays GAS in healthy human subjects. Correlation analysis of data obtained from ingestion of the caffeine solution revealed an association between the magnitude of the GAS response and the perceived bitterness, suggesting a functional role of oral TAS2Rs in GAS. Expression of TAS2Rs, including cognate TAS2Rs for caffeine, was shown in human gastric epithelial cells of the corpus/fundus and in HGT-1 cells, a model for the study of GAS. In HGT-1 cells, various bitter compounds as well as caffeine stimulated proton secretion, whereby the caffeineevoked effect was (i) shown to depend on one of its cognate receptor, TAS2R43, and adenylyl cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of caffeine's bitter taste. This inhibitory effect of HED on caffeine-induced GAS was verified in healthy human subjects. These findings (i) demonstrate that bitter taste receptors in the stomach and the oral cavity are involved in the regulation of GAS and (ii) suggest that bitter tastants and bittermasking compounds could be potentially useful therapeutics to regulate gastric pH.gastric acid secretion | caffeine | homoeriodictyol | bitter taste receptors | TAS2Rs

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mentioning

confidence: 99%

Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells

Liszt

Ley

Lieder

et al. 2017

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

186

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“…[5][6][7][8] Recently, TAS2Rs have been found not only on the tongue but also in the small intestine, stomach, and trachea of mammals. [9][10][11][12] In the digestive tract, TAS2Rs are expressed in the endocrine cells of intestinal epithelial tissues and are known to participate in the secretion of incretins such as glucagon-like peptide-1 (GLP-1) and CCK. [13][14][15] Furthermore, it has been reported that bitter substances, such as denatonium, bind to tracheal smooth muscle, resulting in contraction of the bronchial tube.…”

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confidence: 99%

The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins

Yamazaki

Sagisaka

Ikeda

et al. 2014

Bioscience, Biotechnology, and Biochemistry

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We purified several hundred mgs of four major theaflavins (theaflavin, theaflavin-3-O-gallate, theaflavin-3′-O-gallate, and theaflavin-3,3′-O-digallate). Among the 25 hTAS2Rs expressed in HEK293T cells, hTAS2R39 and hTAS2R14 were activated by theaflavins. Both hTAS2R39 and hTAS2R14 responded to theaflavin-3′-O-gallate. In addition, hTAS2R39 was activated by theaflavin and theaflavin-3,3′-O-gallate, but not by theaflavin-3-O-gallate. In contrast, hTAS2R14 responded to theaflavin-3-O-gallate.

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“…However, many previous immunohistochemical studies solely adopt the conventional "negative control" by either omitting or blocking the primary antibody prior to staining (Ruiz-Avila et al 1995;Haga and Yoshie 2010;Shin et al 2010;Singh et al 2011;Son et al 2011;Dehkordi et al 2012). Peptide blocking might just confirm that the primary antibody is specific for the target peptide sequence (not the entire protein), which is competing against the immune peptide for binding to the primary antibody.…”

Section: Discussionmentioning

confidence: 99%

“…Haga and Yoshie (2010) demonstrated that changes in tissue conditions affected antigen preservation and thus resulted in an altered appearance of gustducinstained taste cells in rat tongues. The existing studies that report on the presence of taste receptors and/or gustducin in the brain (Ren et al 2009;Shin et al 2010;Singh et al 2011;Dehkordi et al 2012) and retina (Son et al 2011) were carried out exclusively on frozen sections. Frozen sectioning protocols however, may bring practical shortcomings to the samples, including degradation, autolysis and diffusion of the proteins, as well as compromised morphological features (Shi et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Non-specific Immunostaining by a Rabbit Antibody against Gustducin α Subunit in Mouse Brain

Xiong

Redding

Chen

et al. 2014

J Histochem Cytochem.

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SummaryGustducin is a guanosine nucleotide-binding protein functionally coupled with taste receptors and thus originally identified in taste cells of the tongue. Recently, bitter taste receptors and gustducin have been detected in the airways, digestive tracts and brain. The existing studies showing taste receptors and gustducin in the brain were carried out exclusively on frozen sections. In order to avoid the technical shortcomings associated with frozen sectioning, we performed immunofluorescence staining using vibratome-cut sections from mouse brains. Using a rabbit gustducin antibody, we could not detect neurons or astrocytes as reported previously. Rather, we found dense fibers in the nucleus accumbens and periventricular areas. We assumed these staining patterns to be specific after confirmation with conventional negative control staining. For the verification of this finding, we stained gustducin knockout mouse brain and tongue sections with the same rabbit gustducin antibody. Whereas negative staining was confirmed in the tongue, intensive fibers were constantly stained in the brain. Moreover, immunostaining with a goat gustducin antibody could not demonstrate the fibers in the brain tissue. The present study implies a cross immunoreaction that occurs with the rabbit gustducin antibody in mouse brain samples, suggesting that the conventional negative controls may not be sufficient when an immunostaining pattern is to be verified. (J Histochem Cytochem 63:79-87, 2015)

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Functional bitter taste receptors are expressed in brain cells

Cited by 153 publications

References 30 publications

Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells

Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells

The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins

Non-specific Immunostaining by a Rabbit Antibody against Gustducin α Subunit in Mouse Brain

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