Taste Receptors in the Gastrointestinal Tract. I. Bitter taste receptors and α-gustducin in the mammalian gut

2006 ◽  
Vol 291 (2) ◽  
pp. G171-G177 ◽  
Author(s):  
Enrique Rozengurt
Keyword(s):  
Bitter Taste ◽  
Critical Role ◽  
Taste Receptor ◽  
Caloric Intake ◽  
Taste Receptors ◽  
Neural Pathways ◽  
Gi Tract ◽  
Lingual Epithelium ◽  
Molecular Sensing ◽  
Pancreatic Insulin

Molecular sensing by gastrointestinal (GI) cells plays a critical role in the control of multiple fundamental functions in digestion and also initiates hormonal and/or neural pathways leading to the regulation of caloric intake, pancreatic insulin secretion, and metabolism. Molecular sensing in the GI tract is also responsible for the detection of ingested harmful drugs and toxins, thereby initiating responses critical for survival. The initial recognition events and mechanism(s) involved remain incompletely understood. The notion to be discussed in this article is that there are important similarities between the chemosensensory machinery elucidated in specialized neuroepithelial taste receptor cells of the lingual epithelium and the molecular transducers localized recently in enteroendocrine open GI cells that sense the chemical composition of the luminal contents of the gut.

Taste Receptors in the Gastrointestinal Tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing

2007 ◽  
Vol 292 (2) ◽  
pp. G457-G461 ◽  
Author(s):  
Catia Sternini
Keyword(s):  
Gastrointestinal Tract ◽  
Bitter Taste ◽  
Clinical Importance ◽  
Signaling Molecules ◽  
Taste Receptors ◽  
Neural Pathways ◽  
Gastrointestinal Mucosa ◽  
Protein Subunits ◽  
Disease States ◽  
Functional Implications

Changes in the luminal contents of the gastrointestinal tract modulate gastrointestinal functions, including absorption of nutrients, food intake, and protection against harmful substances. The current notion is that mucosal enteroendocrine cells act as primary chemoreceptors by releasing signaling molecules in response to changes in the luminal environment, which in turn activate nerve terminals. The recent discovery that taste receptors and G protein subunits α-gustducin and α-transducin, involved in gustatory signal transduction, are expressed in the gastrointestinal mucosa supports the concept of a chemosensory machinery in the gastrointestinal tract. An understanding of luminal sensing processes responsible for the generation of the appropriate functional response to specific nutrients and nonnutrients is of clinical importance since aberrant or unsteady responses to changes in luminal contents might result in disease states ranging from intoxication to feeding disorders and inflammation. The purpose of this theme article is to discuss the functional implications of bitter taste signaling molecules in the gastrointestinal tract deduced by their localization in selected populations of epithelial cells and their relationship with neural pathways responsible for the generation of specific responses to luminal contents.

scholarly journals Taste receptor polymorphisms and longevity: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Danilo Di Bona ◽  
Alberto Malovini ◽  
Giulia Accardi ◽  
Anna Aiello ◽  
Giuseppina Candore ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bitter Taste ◽  
Meta Analysis ◽  
Taste Receptor ◽  
The Other ◽  
Analytic Approach ◽  
Taste Receptors ◽  
South Italy ◽  
Physiological Processes ◽  
Different Populations

AbstractBitter taste receptors (TAS2R) are involved in a variety of non-tasting physiological processes, including immune-inflammatory ones. Therefore, their genetic variations might influence various traits. In particular, in different populations of South Italy (Calabria, Cilento, and Sardinia), polymorphisms of TAS2R16 and TAS238 have been analysed in association with longevity with inconsistent results. A meta-analytic approach to quantitatively synthesize the possible effect of the previous variants and, possibly, to reconcile the inconsistencies has been used in the present paper. TAS2R38 variants in the Cilento population were also analysed for their possible association with longevity and the obtained data have been included in the relative meta-analysis. In population from Cilento no association was found between TAS2R38 and longevity, and no association was observed as well, performing the meta-analysis with data of the other studies. Concerning TAS2R16 gene, instead, the genotype associated with longevity in the Calabria population maintained its significance in the meta-analysis with data from Cilento population, that, alone, were not significant in the previously published study. In conclusion, our results suggest that TAS2R16 genotype variant is associated with longevity in South Italy.

scholarly journals In Silico Molecular Study of Tryptophan Bitterness

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4623
Author(s):  
Antonella Di Pizio ◽  
Alessandro Nicoli
Keyword(s):  
Amino Acid ◽  
Molecular Modeling ◽  
In Silico ◽  
Essential Amino Acid ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Molecular Study ◽  
Taste Receptors ◽  
Bitter Taste Receptor ◽  
The Core

Tryptophan is an essential amino acid, required for the production of serotonin. It is the most bitter amino acid and its bitterness was found to be mediated by the bitter taste receptor TAS2R4. Di-tryptophan has a different selectivity profile and was found to activate three bitter taste receptors, whereas tri-tryptophan activated five TAS2Rs. In this work, the selectivity/promiscuity profiles of the mono-to-tri-tryptophans were explored using molecular modeling simulations to provide new insights into the molecular recognition of the bitter tryptophan. Tryptophan epitopes were found in all five peptide-sensitive TAS2Rs and the best tryptophan epitope was identified and characterized at the core of the orthosteric binding site of TAS2R4.

scholarly journals Activation of specific bitter taste receptors by olive oil phenolics and secoiridoids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng Cui ◽  
Bohan Chen ◽  
Keman Xu ◽  
Aimilia Rigakou ◽  
Panagiotis Diamantakos ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Olive Oil ◽  
Bitter Taste ◽  
Virgin Olive Oil ◽  
Taste Receptor ◽  
Extra Virgin Olive Oil ◽  
Milling Process ◽  
Functional Assay ◽  
Taste Receptors ◽  
Bitter Taste Receptors

AbstractExtra-virgin olive oil (EVOO) is a critical component of the Mediterranean diet, which has been found beneficial to human health. Bitterness is often positively associated with the presence of phenolic compounds in EVOO. There are twenty-five bitter taste receptors (TAS2Rs) in humans, each of which responds to specific bitter tastants. The identity of phenolic compounds and the bitter taste receptors they stimulate remain unknown. In this study, we isolated 12 phenolic and secoiridoid compounds from the olive fruit and the oil extracted from it, and tested their ability to stimulate bitter taste receptor activity, using a calcium mobilization functional assay. Our results showed that seven out of twelve studied compounds activated TAS2R8, and five of them activated TAS2R1, TAS2R8, and TAS2R14. The phenolic compounds oleuropein aglycon and ligstroside aglycon were the most potent bitter tastants in olive oil. TAS2R1 and TAS2R8 were the major bitter taste receptors activated most potently by these phenolic compounds. The results obtained here could be utilized to predict and control the bitterness of olive oil based on the concentration of specific bitter phenolics produced during the milling process of olives.

Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands

2008 ◽  
Vol 294 (1) ◽  
pp. R33-R38 ◽  
Author(s):  
Shuzhen Hao ◽  
Catia Sternini ◽  
Helen E. Raybould
Keyword(s):  
G Protein ◽  
Bitter Taste ◽  
Peptide Yy ◽  
Receptor Gene ◽  
Taste Receptor ◽  
Vagal Afferents ◽  
Intragastric Administration ◽  
Gustatory System ◽  
Gi Tract ◽  
Α Subunit

G-protein-coupled receptors signaling bitter taste (T2Rs) in the oral gustatory system and the α-subunit of the taste-specific G-protein gustducin are expressed in the gastrointestinal (GI) tract. α-Subunit of the taste-specific G-protein gustducin colocalizes with markers of enteroendocrine cells in human and mouse GI mucosa, including peptide YY. Activation of T2Rs increases cholecystokinin (CCK) release from the enteroendocrine cell line, STC-1. The aim of this study was to determine whether T2R agonists in the GI tract activate neurons in the nucleus of the solitary tract (NTS) and whether this activation is mediated by CCK and peptide YY acting at CCK1 and Y2 receptors. Immunocytochemistry for the protooncogene c-Fos protein, a marker for neuronal activation, was used to determine activation of neurons in the midregion of the NTS, the region where vagal afferents from the GI tract terminate. Intragastric administration of the T2R agonist denatonium benzoate (DB), or phenylthiocarbamide (PTC), or a combination of T2R agonists significantly increased the number of Fos-positive neurons in the mid-NTS; subdiaphragmatic vagotomy abolished the NTS response to the mixture of T2R agonists. Deletion of CCK1 receptor gene or blockade of CCK1 receptors with devazepide abolishes the activation of NTS neurons in response to DB, but had no effect on the response to PTC. Administration of the Y2 receptor antagonist BIIE0246 blocks the activation of NTS neurons to DB, but not PTC. These findings suggest that activation of neurons in the NTS following administration of T2R agonists to the GI tract involves CCK1 and Y2 receptors located on vagal afferent terminals in the gut wall. T2Rs may regulate GI function via release of regulatory peptides and activation of the vagal reflex pathway.

scholarly journals Bitter taste receptors of the common vampire bat are functional and show conserved responses to metal ions in vitro

2021 ◽  
Vol 288 (1947) ◽  
Author(s):  
Florian Ziegler ◽  
Maik Behrens
Keyword(s):  
Metal Ions ◽  
Bitter Taste ◽  
Prey Selection ◽  
Taste Receptor ◽  
Food Sources ◽  
Taste Receptors ◽  
Vampire Bats ◽  
Bitter Taste Receptors ◽  
Vampire Bat

The bitter taste sensation is important to warn mammals of the ingestion of potentially toxic food compounds. For mammals, whose nutrition relies on highly specific food sources, such as blood in the case of vampire bats, it is unknown if bitter sensing is involved in prey selection. By contrast to other bat species, vampire bats exhibit numerous bitter taste receptor pseudogenes, which could point to a decreased importance of bitter taste. However, electrophysiological and behavioural studies suggest the existence of functional bitter taste transmission. To determine the agonist spectra of the three bitter taste receptors that are conserved in all three vampire bat species, we investigated the in vitro activation of Desmodus rotundus T2R1, T2R4 and T2R7. Using a set of 57 natural and synthetic bitter compounds, we were able to identify agonists for all three receptors. Hence, we confirmed a persisting functionality and, consequently, a putative biological role of bitter taste receptors in vampire bats. Furthermore, the activation of the human TAS2R7 by metal ions is shown to be conserved in D. rotundus .

scholarly journals Interactions between Bitter Taste, Diet and Dysbiosis: Consequences for Appetite and Obesity

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1336 ◽  
Author(s):  
Alexandria Turner ◽  
Martin Veysey ◽  
Simon Keely ◽  
Christopher Scarlett ◽  
Mark Lucock ◽  
...  
Keyword(s):  
Energy Harvesting ◽  
Bitter Taste ◽  
Disease Risk ◽  
Health Concern ◽  
Taste Receptors ◽  
Gi Tract ◽  
Potential Link ◽  
Modifiable Factor ◽  
The Subject

The type 2 family of taste receptors (T2Rs) detect and respond to bitter tastants. These receptors are expressed throughout the gastrointestinal (GI) tract, with location dependant roles. In the oral cavity, T2Rs are involved in the conscious perception of bitter tastants, while in the lower GI tract they have roles in chemoreception and regulation of GI function. Through these diverse roles, these receptors may be involved in modulating appetite and diet, with consequences for weight regulation and obesity. Interestingly, the concentration of T2Rs in the GI tract is greatest in the large intestine, the organ with the densest colonisation of bacteria. The gut microbiome has been the subject of intense research, as a plethora of roles linking microbiota to human health continue to be uncovered. Of particular interest is the microbial signature associated with obesity. Obesity is a leading health concern, and advances in our understanding of this disease are needed. Diet is a known modifiable factor in the development of obesity. However, diet only partially explains disease risk. Changes in microbial energy harvesting by the microbiota plays a role in obesity, and the composition of these energy harvesting populations may be controlled by taste receptors. This review explores T2Rs as a potential link between obesity and the human GI microbiome.

scholarly journals Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota

2011 ◽  
Vol 107 (5) ◽  
pp. 621-630 ◽  
Author(s):  
T. D. Swartz ◽  
F. A. Duca ◽  
T. de Wouters ◽  
Y. Sakar ◽  
M. Covasa
Keyword(s):  
Gut Microbiota ◽  
Food Consumption ◽  
Intestinal Epithelium ◽  
Sucrose Solution ◽  
Critical Role ◽  
Taste Receptor ◽  
Sweet Taste ◽  
High Concentration ◽  
Lingual Epithelium

The chemosensory components shared by both lingual and intestinal epithelium play a critical role in food consumption and the regulation of intestinal functions. In addition to nutrient signals, other luminal contents, including micro-organisms, are important in signalling across the gastrointestinal mucosa and initiating changes in digestive functions. A potential role of gut microbiota in influencing food intake, energy homeostasis and weight gain has been suggested. However, whether gut microbiota modulates the expression of nutrient-responsive receptors and transporters, leading to altered food consumption, is unknown. Thus, we examined the preference for nutritive (sucrose) and non-nutritive (saccharin) sweet solutions in germ-free (GF, C57BL/6J) mice compared with conventional (CV, C57BL/6J) control mice using a two-bottle preference test. Then, we quantified mRNA and protein expression of the sweet signalling protein type 1 taste receptor 3 (T1R3) and α-gustducin and Na glucose luminal transporter-1 (SGLT-1) of the intestinal epithelium of both CV and GF mice. Additionally, we measured gene expression of T1R2, T1R3 and α-gustducin in the lingual epithelium. We found that, while the preference for sucrose was similar between the groups, GF mice consumed more of the high concentration (8 %) of sucrose solution than CV mice. There was no difference in either the intake of or the preference for saccharin. GF mice expressed significantly more T1R3 and SGLT-1 mRNA and protein in the intestinal epithelium compared with CV mice; however, lingual taste receptor mRNA expression was similar between the groups. We conclude that the absence of intestinal microbiota alters the expression of sweet taste receptors and GLUT in the proximal small intestine, which is associated with increased consumption of nutritive sweet solutions.

scholarly journals Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Davide S. Risso ◽  
Massimo Mezzavilla ◽  
Luca Pagani ◽  
Antonietta Robino ◽  
Gabriella Morini ◽  
...  
Keyword(s):  
Natural Selection ◽  
Bitter Taste ◽  
Balancing Selection ◽  
Receptor Gene ◽  
Critical Role ◽  
Taste Receptor ◽  
Bitter Taste Receptor ◽  
Worldwide Distribution ◽  
Selective Forces ◽  
Bitter Taste Receptor Gene

Abstract The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

scholarly journals Neural Transmission from Oropharyngeal Bitter Receptors to the Medulla is Partially or Completely Labelled-Line

2016 ◽  
Vol 11 (8) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Michael K McMullen
Keyword(s):  
Bitter Taste ◽  
Cell Receptor ◽  
Cell Physiology ◽  
Taste Receptors ◽  
Neural Pathways ◽  
Cephalic Phase ◽  
Autonomic Reflexes ◽  
Neural Transmission ◽  
Bitter Taste Receptors ◽  
The Impact

The ground breaking advances in taste cell receptor cell physiology over the last 20 years have established a functional basis which enables neural pathways to be mapped. There is only one, or perhaps several, types of taste receptors for salt, sour, sweet and umami (meaty) tastes and stimulation of each receptor type elicits responses in different cognitive regions. These findings support the labelled-line neural pathway model. In contrast, there are 25 types of the bitter taste receptors which all produce the same cognitive sensation, a finding which supports the across-fiber pattern model. This paper compiles the findings of several human studies investigating the impact of bitter tastants on postprandial hemodynamics, to demonstrate that diverse bitter tastants are capable of eliciting a range of characteristic reflex cephalic phase responses in the autonomic and cardiovascular systems. These findings indicate that neural pathways from the oropharyngeal bitter taste receptors to the nucleus of the solitary tract are either partially or completely labelled-line. Consequently, the hedonics of a bitter tastant are not an accurate indicator of the cephalic phase responses elicited by the tastant. The finding that secondary metabolites present in dietary condiments modulate autonomic activity and in particular postprandial hemodynamics is novel and adds a new dimension to our understanding of the ways in which humans are influenced by their diet, both in health and disease. These findings suggest that condiments play a role in food digestion, unrelated to their hedonistic qualities. Consequently, condiments may be of significance to those with digestive disorders and especially for diabetics experiencing gastroparesis and/or postprandial hypotension. Additionally, the findings suggest a noninvasive method to assess the integrity of multiple neural pathways. For investigators exploring the effect of condiments on autonomic reflexes, traditional cuisines may be a valuable source as they are full of uncharted human recordings.

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