Differential Activation of May Recover Ability to Taste Propylthiouracil for Some AVI Homozygotes.

Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake.

LRBA, a BEACH protein mutated in human immune deficiency, is widely expressed in epithelia, exocrine and endocrine glands, and neurons.

Mutations in LRBA, a BEACH domain protein, cause severe immune deficiency in humans. LRBA is expressed in many tissues and organs according to biochemical analysis, but little is known about its cellular and subcellular localization, and its deficiency phenotype outside the immune system. By LacZ histochemistry of Lrba gene-trap mice, we performed a comprehensive survey of LRBA expression in numerous tissues, detecting it in many if not all epithelia, in exocrine and endocrine cells, and in subpopulations of neurons.

Comprehensive structure-activity-relationship studies of sensory active compounds in licorice (Glycyrrhiza glabra).

Licorice saponins, the main constituents of Glycyrrhiza glabra L. roots, are highly appreciated by the consumer for their pleasant sweet and long lasting licorice taste. The objective of the present study was to understand the molecular features that contribute to bitter, sweet and licorice sensation of licorice roots, and whether individual compounds elicit more than one of these sensations.

Sensory-Guided Multidimensional Exploration of Antisweet Principles from (Retz) Schult.

We report on activity-guided investigation of the key antisweet principles of . Orosensory-guided fractionation by means of solid phase extraction, preparative 2D-LC, and semipreparative HPLC followed by accurate MS and 1D/2D NMR experiments revealed six known and three previously unknown gymnemic acids as the key constituents of seven highly sensory-active fractions. Localized via a modified comparative taste dilution analysis (cTDA) and taste modulation probability (TMP) based screening techniques, a strong intrinsic bitterness was also observed for gymnemic acids.

At the Root of T2R Gene Evolution: Recognition Profiles of Coelacanth and Zebrafish Bitter Receptors.

The careful evaluation of food is important for survival throughout the animal kingdom, and specialized chemoreceptors have evolved to recognize nutrients, minerals, acids, and many toxins. Vertebrate bitter taste, mediated by the taste receptor type 2 (T2R) family, warns against potentially toxic compounds. During evolution T2R receptors appear first in bony fish, but the functional properties of bony fish T2R receptors are mostly unknown.

Sodium Imbalance in Mice Results Primarily in Compensatory Gene Regulatory Responses in Kidney and Colon, but Not in Taste Tissue.

Renal excretion and sodium appetite provide the basis for sodium homeostasis. In both the kidney and tongue, the epithelial sodium channel (ENaC) is involved in sodium uptake and sensing. The diuretic drug amiloride is known to block ENaC, producing a mild natriuresis.

Segregated Expression of ENaC Subunits in Taste Cells.

Salt taste is one of the 5 basic taste qualities. Depending on the concentration, table salt is perceived either as appetitive or aversive, suggesting the contribution of several mechanisms to salt taste, distinguishable by their sensitivity to the epithelial sodium channel (ENaC) blocker amiloride. A taste-specific knockout of the α-subunit of the ENaC revealed the relevance of this polypeptide for low-salt transduction, whereas the response to other taste qualities remained normal.

Intragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men.

The rate of gastric emptying and the release of gastrointestinal (GI) hormones are major determinants of postprandial blood-glucose concentrations and energy intake. Preclinical studies suggest that activation of GI bitter-taste receptors potently stimulates GI hormones, including glucagon-like peptide-1 (GLP-1), and thus may reduce postprandial glucose and energy intake. We evaluated the effects of intragastric quinine on the glycemic response to, and the gastric emptying of, a mixed-nutrient drink and the effects on subsequent energy intake in healthy men.

Taste receptor function.

This chapter summarizes the available data about taste receptor functions and their role in perception of food with emphasis on the human system. In addition we illuminate the widespread presence of these receptors throughout the body and discuss some of their extraoral functions. Finally, we describe clinical aspects where taste receptor signaling could be relevant.

Dual binding mode of "bitter sugars" to their human bitter taste receptor target.

The 25 human bitter taste receptors (hTAS2Rs) are responsible for detecting bitter molecules present in food, and they also play several physiological and pathological roles in extraoral compartments. Therefore, understanding their ligand specificity is important both for food research and for pharmacological applications. Here we provide a molecular insight into the exquisite molecular recognition of bitter β-glycopyranosides by one of the members of this receptor subclass, hTAS2R16.

Effects of Intraduodenal Infusion of the Bitter Tastant, Quinine, on Antropyloroduodenal Motility, Plasma Cholecystokinin, and Energy Intake in Healthy Men.

Background/aims: Nutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation) contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shown in cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressed throughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. This study aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energy intake.

The human bitter taste receptor TAS2R7 facilitates the detection of bitter salts.

The human sense of taste is devoted to the analysis of the chemical composition of food prior to ingestion. Among the five basic taste qualities bitter taste perception is believed to avoid ingestion of potentially toxic substances. The receptors facilitating the detection of hundreds of chemically different bitter compounds belong to the taste 2 receptor (TAS2R) family, which are part of the G protein-coupled superfamily.

A role for taste receptors in (neuro)endocrinology?

The sense of taste is positioned at the forefront when it comes to the interaction of our body with foodborne chemicals. However, the role of our taste system, and in particular its associated taste receptors, is not limited to driving food preferences leading to ingestion or rejection before other organs take over responsibility for nutrient digestion, absorption and metabolic regulation. Taste sensory elements do much more.

The Crystal Structure of Gurmarin, a Sweet Taste-Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition.

Gurmarin is a highly specific sweet taste-suppressing protein in rodents that is isolated from the Indian plant Gymnema sylvestre. Gurmarin consists of 35 amino acid residues containing 3 intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.

Intestinal bitter taste receptor activation alters hormone secretion and imparts metabolic benefits.

Objectives: Extracts of the hops plant have been shown to reduce weight and insulin resistance in rodents and humans, but elucidation of the mechanisms responsible for these benefits has been hindered by the use of heterogeneous hops-derived mixtures. Because hop extracts are used as flavoring agents for their bitter properties, we hypothesized that bitter taste receptors (Tas2rs) could be mediating their beneficial effects in metabolic disease. Studies have shown that exposure of cultured enteroendocrine cells to bitter tastants can stimulate release of hormones, including glucagon-like peptide 1 (GLP-1).

Human Bitter Taste Receptors Are Activated by Different Classes of Polyphenols.

Polyphenols may contribute directly to plant-based foodstuffs flavor, in particular to astringency and bitterness. In this work, the bitterness of a small library of polyphenols from different classes [procyanidin dimers type B, ellagitannins (punicalagin, castalagin, and vescalagin) and phenolic acid ethyl esters (protocatechuic, ferulic, and vanillic acid ethyl esters] was studied by a cell-based assay. The bitter taste receptors (TAS2Rs) activated by these polyphenols and the half-maximum effective concentrations (EC) of each agonist-TAS2Rs pair were determined.

Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14.

Background: In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste.

Proton Transport Chains in Glucose Metabolism: Mind the Proton.

The Embden-Meyerhof-Parnas (EMP) pathway comprises eleven cytosolic enzymes interacting to metabolize glucose to lactic acid [CHCH(OH)COO]. Glycolysis is largely considered as the conversion of glucose to pyruvate (CHCOCOO). We consider glycolysis to be a cellular process and as such, transporters mediating glucose uptake and lactic acid release and enable the flow of metabolites through the cell, must be considered as part of the EMP pathway.

Tastant-Evoked Arc Expression in the Nucleus of the Solitary Tract and Nodose/Petrosal Ganglion of the Mouse Is Specific for Bitter Compounds.

Despite long and intense research, some fundamental questions regarding representation of taste information in the brain still remain unanswered. This might in part be due to shortcomings of the established methods that limit the researcher either to thorough characterization of few elements or to analyze the response of the entirety of neurons to only one stimulus. To overcome these restrictions, we evaluate the use of the immediate early gene Arc as a neuronal activity marker in the early neural structures of the taste pathway, the nodose/petrosal ganglion (NPG) and the nucleus of the solitary tract (NTS).

Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.

Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors ( taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste.

Structure-Function Relationships of Olfactory and Taste Receptors.

The field of chemical senses has made major progress in understanding the cellular mechanisms of olfaction and taste in the past 2 decades. However, the molecular understanding of odor and taste recognition is still lagging far behind and will require solving multiple structures of the relevant full-length receptors in complex with native ligands to achieve this goal. However, the development of multiple complimentary strategies for the structure determination of G protein-coupled receptors (GPCRs) makes this goal realistic.

Amino acid sensing in hypothalamic tanycytes via umami taste receptors.

Objective: Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety.

Methods: Ca imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids.

Genetic Labeling of Car4-expressing Cells Reveals Subpopulations of Type III Taste Cells.

Carbonic anhydrases form an enzyme family of 16 members, which reversibly catalyze the hydration of carbon dioxide to bicarbonate and protons. In lung, kidney, and brain, presence of carbonic anhydrases is associated with protons and bicarbonate transport in capillary endothelium of lung, reabsorption of bicarbonate in proximal renal tubules, and extracellular buffering. In contrast, their role in taste is less clear.

Blends of Non-caloric Sweeteners Saccharin and Cyclamate Show Reduced Off-Taste due to TAS2R Bitter Receptor Inhibition.

Non-caloric sweeteners are widely used for the formulation of calorie-reduced beverages for health-conscious consumers. However, disadvantages such as undesired off-tastes limit the use of non-nutritive sweeteners. Therefore, the food industry is constantly searching for novel sweeteners and frequently resorts to using blends combining non-caloric sweeteners in a single formulation.

Bitter substances from plants used in traditional Chinese medicine exert biased activation of human bitter taste receptors.

The number and variety of bitter compounds originating from plants are vast. Whereas some bitter chemicals are toxic and should not be ingested, other compounds exhibit health beneficial effects, which is manifest in the cross-cultural believe that the bitterness of medicine is correlated with the desired medicinal activity. The bitter taste receptors in the oral cavity serve as sensors for bitter compounds and, as they are expressed in numerous extraoral tissues throughout the body, may also be responsible for some physiological effects exerted by bitter compounds.