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Relationship of papillae number to bitter intensity of quinine and PROP within and between individuals.

Subjects were asked to assess the bitterness of one 6-n-propyl-2-thiouracil (PROP) and two quinine HCl (QHCl) concentrations presented via filter papers of varying sizes. The number of taste papillae stimulated by these filter papers was counted in each individual. Whole mouth sensitivity to PROP was determined in a separate session. In support of other demonstrations of spatial summation, these data indicated that perceived bitterness intensity increased as a function of area of stimulation within subjects. Between subjects, there was a significant trend for the perceived bitterness of PROP to increase with the lingual density of fungiform papillae, although this trend was highly variable and was only demonstrable among those who showed at least moderate sensitivity to PROP. On the other hand, the number of stimulated fungiform papillae failed to account for individual differences in perceived bitterness of QHCl.

Adult↗

Improvement of the bitter taste of amino acids through the transpeptidation reaction of bacterial gamma-glutamyltranspeptidase.

The tastes of several bitter amino acids and their gamma-glutamyl derivatives were compared. The bitterness of Phe, Val, Leu, and His was reduced, sourness was produced, and preferences were increased by gamma-glutamylization. Because the effect of gamma-glutamylization of bitter amino acids was most obvious for Phe, which is an atypical bitter amino acid, an enzymatic method for the synthesis of gamma-glutamylphenylalanine (gamma-Glu-Phe) involving bacterial gamma-glutamyltranspeptidase was developed. The optimum reaction conditions were 200 mM Gln, 200 mM Phe, and 0.5 unit/mL GGT, pH 10.4. After 1.5-h of incubation at 37 degrees C, 140 mM gamma-Glu-Phe was obtained, the yield being 70%. gamma-Glu-Phe was purified on a Dowex 1x8 column and then identified by NMR.

Amino Acids↗

Relationships of sweet, bitter, and roasted peanut sensory attributes with carbohydrate components in peanuts.

Certain roasted peanut quality sensory attributes have been shown to be heritable. Currently the only means of measuring these traits is the use of a trained sensory panel. This is a costly and time-consuming process. It is desirable, from a cost, time, and sample size perspective, to find other methodologies for estimating these traits. Because sweetness is the most heritable trait and it has a significant positive relationship to the roasted peanut trait, the possible relationships between heritable sensory traits and 18 carbohydrate components (inositol, glucose, fructose, sucrose, raffinose, stachyose, and 12 unknown peaks) in raw peanuts from 52 genotypes have been investigated. Previously reported correlations among sweet, bitter, and roasted peanut attributes were evident in this study as well. Where there was positive correlation of total sugars with sweetness, there also was positive correlation of total sugars with roasted peanut attribute and negative correlation of total sugars with bitterness and astringency. The expected generalized relationship of total sugars or sucrose to sweetness could not be established because the relationship was not the same across all market-types. Further work is needed to determine the nature of the chemical components related to the bitter principle, which appear to modify the sweet response and interfere with the sensory perception of sweetness, particularly in the Virginia market-type. Also, certain carbohydrate components showed significant relationships with sensory attributes in one market-type and not another. These differential associations demonstrate the complexity of the interrelationships among sweet, bitter, and roasted peanut sensory attributes. Within two market-types it is possible to improve the efficiency of selection for sweetness and roasted peanut quality by assaying for total carbohydrates. On the basis of the regression values the greatest efficiency would occur in the fastigiate market-type and then the runner.

Arachis↗

Quantitative structure-activity relationships of the bitter thresholds of amino acids, peptides, and their derivatives.

Bitter thresholds of a total of 93 amino acids, peptides, and their derivatives were analyzed quantitatively by use of hydrophobicity parameters reported for amino acid side chains and those for the whole molecules estimated from partition coefficients obtained experimentally. We also explored the steric parameters that best explained the variation in the intensity of bitterness attributable to the molecular shape. The results showed that the total length along the zigzag peptide backbone chain of the molecule is an important factor. The bitterness of nonzwitterionic N-acyl and ester derivatives and that of neutral N-acyl ester derivatives were expressed by a single, common equation together with those of zwitterionic amino acids and peptides. Thus the interaction via the charge with the receptor site was probably not an indispensible factor for triggering of the bitter sensation. This study, together with earlier ones, may serve as a prototype of approaches toward unraveling structure-activity relationships of complex molecules like amino acids, peptides, and their derivatives that are of medicinal or agricultural importance.

Amino Acids↗

Ultraviolet spectroscopic estimation of microenvironments and bitter tastes of oxyphenonium bromide in cyclodextrin solutions.

The UV absorbance and bitter taste of oxyphenonium bromide (OB), an antiacetylcholine drug, in cyclodextrin (CD) solutions are measured, and the local environment of the binding site and the reduction of the bitter taste intensity are quantitatively estimated from the UV data. The UV spectrum of OB is changed with the addition of alpha-, beta-, and gamma-CD, because the phenyl group of OB is included into the CD cavity. The maximum wavelength, lambda(max), senses environmental changes of OB best among several spectral characteristics. From comparison of lambda(max) between a CD solution and the reference ethanol-water and dioxane-water systems, the dielectric constant of the binding site is evaluated. This value leads us to estimate the microenvironment and structure of the binding site. The suppression of the bitter taste of 4 mM OB by CDs is in the increasing order alpha-CD < gamma-CD < beta-CD. The extent of this suppression can be quantitatively predicted from the UV absorbance by assuming that the free OB molecule alone exhibits the bitter taste, regardless of the kind and concentration of CD. Some implications and limitations of the present approach are discussed.

Cyclodextrins↗

Transduction of bitter and sweet taste by gustducin.

Several lines of evidence suggest that both sweet and bitter tastes are transduced via receptors coupled to heterotrimeric guanine-nucleotide-binding proteins (G proteins). Gustducin is a taste receptor cell (TRC)-specific G protein that is closely related to the transducins. Gustducin and rod transducin, which is also expressed in TRCs, have been proposed to couple bitter-responsive receptors to TRC-specific phosphodiesterases to regulate intracellular cyclic nucleotides. Here we investigate gustducin's role in taste transduction by generating and characterizing mice deficient in the gustducin alpha-subunit (alpha-gustducin). As predicted, the mutant mice showed reduced behavioural and electrophysiological responses to bitter compounds, whereas they were indistinguishable from wild-type controls in their responses to salty and sour stimuli. Unexpectedly, mutant mice also exhibited reduced behavioural and electrophysiological responses to sweet compounds. Our results suggest that gustducin is a principal mediator of both bitter and sweet signal transduction.

Animals↗

Computational studies of ligand-receptor interactions in bitter taste receptors.

Phenylthiocarbamide tastes intensely bitter to some individuals, but others find it completely tasteless. Recently, it was suggested that phenylthiocarbamide elicits bitter taste by interacting with a human G protein-coupled receptor (hTAS2R38) encoded by the PTC gene. The phenylthiocarbamide nontaster trait was linked to three single nucleotide polymorphisms occurring in the PTC gene. Using the crystal structure of bovine rhodopsin as template, we generated the 3D structure of hTAS2R38 bitter taste receptor. We were able to map on the receptor structure the amino acids affected by the genetic polymorphisms and to propose molecular functions for two of them that explained the emergence of the nontaster trait. We used molecular docking simulations to find that phenylthiocarbamide exhibited a higher affinity for the target receptor than the structurally similar molecule 6-n-propylthiouracil, in line with recent experimental studies. A 3D model was constructed for the hTAS2R16 bitter taste receptor as well, by applying the same protocol. We found that the recently published experimental ligand binding affinity data for this receptor correlated well with the binding scores obtained from our molecular docking calculations.

Animals↗

Taste sensitivity to 6-n-propylthiouracil predicts acceptance of bitter-tasting spinach in 3-6-y-old children.

BACKGROUND: Understanding what motivates the preference for and selection of foods has important health implications. Research suggests that the phytochemicals present in green leafy vegetables contain anticarcinogenic properties. As a result of the bitter taste of phytochemical compounds, however, foods containing these are often not well accepted, particularly by children. OBJECTIVE: We aimed to study the relation between sensitivity to the bitter taste of 6-n-propylthiocuracil (PROP) and acceptance of bitter- and strong-tasting foods in 3-6-y-old children. DESIGN: Two independent procedures, a threshold detection and a suprathreshold intensity task, were used to measure individual sensitivity to PROP, and 3 independent tasks were used to assess food acceptance. RESULTS: Sensitivity to the bitter taste of PROP was positively correlated with dislike of the taste of raw spinach (P < 0.05). CONCLUSIONS: The acceptance of spinach may to some extent be mediated by individual taste perception and be predictable via both threshold and suprathreshold measures of PROP taste sensitivity. Furthermore, children as young as 3 y of age can partake in direct investigations of taste, reliably comply with test procedures, and accurately communicate taste perceptions and preferences under study conditions.

Child, Preschool↗

The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium salt) (Na-PMP) on the taste of bitter-sweet stimuli.

The effect of the sweetness inhibitor 2(-4-methoxyphenoxy)propanoic acid (sodium salt) (Na-PMP) on the taste and temporal properties of a range of bitter-sweet stimuli was determined using a trained sensory panel. Na-PMP was found to be an effective inhibitor of the sweetness response of all stimuli tested, reducing both sweetness intensity and persistence. The inhibitor was found to be specific to sweet taste, no reduction in bitterness intensity or persistence was observed at the concentrations of Na-PMP employed in this study. The results therefore do not support the claim of Fuller and Kurtz (1991), that Na-PMP is a potent bitterness inhibitor, but rather support the existence of two distinct receptor sites/loci in sweet and bitter chemoreception.

Adult↗

Genetic sensitivity to 6-n-propylthiouracil (PROP) and hedonic responses to bitter and sweet tastes.

Genetically mediated sensitivity to the bitter taste of 6-n-propylthiouracil (PROP) has been associated with greater acuity for bitter and for some sweet tastes. Thus far, few studies have explored the relationship between PROP taste sensitivity and hedonic responses to bitter and sweet. In this study, 87 normal-weight young women were divided into PROP non-tasters (n = 18), regular tasters (n = 49), and supertasters (n = 20), based on their PROP detection thresholds and the scaling of five suprathreshold solutions of PROP and NaCl. Non-tasters had thresholds > 1.8 x 10(-4) mol/l PROP. Supertasters had thresholds < 3.2 x 10(-5) mol/l PROP and PROP/NaCl ratios > 1.70. As expected, dislike of the bitter taste of PROP was determined by its perceived intensity, which was greater among supertasters than among regular tasters or non-tasters. Significant correlations were observed between PROP taste thresholds and the sum of intensity ratings (r = -0.61) and between summed intensity and summed hedonic ratings (r = -0.80). PROP taste sensitivity was weakly linked to enhanced perception of sweet taste, but did not predict hedonic responses to sucrose or to saccharin solutions. Given that the dislike of PROP solutions is determined by their perceived intensity, hedonic responses to PROP solutions may provide a rapid way of screening for PROP taster status.

Factor Analysis, Statistical↗

Effect of compound sequence on bitterness enhancement.

The nature and occurrence of carry-over effects, i.e. the response to a stimulus is influenced by previous samples, were examined for selected bitter compounds. A time-intensity procedure was used to rate the bitterness of six compounds (caffeine, denatonium benzoate, limonin, naringin, quinine and sucrose octa-acetate). For each subject concentrations of these compounds were determined that were approximately equal in intensity to 1.18 x 10(-5) M limonin. To test carry-over effects of each compound the 36 paired sequences (pairs) were evaluated. Within a session three pairs were tested, between which two-stage rinses were used to remove any effects of the previous pairs. Within a pair only water rinses were used between stimuli. For all compounds carry-over or sensitization effects were observed in which values for maximum intensity, rate of onset and total area under the time-intensity curve were higher for a compound when tested in the second position than in the first. In addition, the degree of sensitization and susceptibility to sensitization were compound-specific. Caffeine increased the bitterness by the largest amount for all other compounds, while it was least affected. Regardless of the compound in the first position, the bitterness of quinine and denatonium were most enhanced.

Administration, Oral↗

Diverse bitter stimuli elicit highly similar patterns of Fos-like immunoreactivity in the nucleus of the solitary tract.

Previous studies have demonstrated that oral stimulation with quinine elicits Fos-like immunoreactivity in the first-order gustatory nucleus, the NST, with a different topographic distribution than sucrose or citric acid. However, it is unknown whether the quinine pattern is unique to this alkaloid or common across bitter stimuli with different chemical structures. Indeed, recent physiological experiments suggest that taste receptor cells and primary afferent neurons may exhibit selectivity for various bitter tastants. The present investigation compared the distribution of FLI in NST following stimulation with three bitter chemicals: QHCl, denatonium and propylthiouracil, stimuli that evoked Ca(2+) currents in almost entirely different sets of receptor cells. The results demonstrate that the quinine pattern is not idiosyncratic but instead generalizes to the other two tastants. Although it remains possible that intermingled but different NST neurons are activated by these stimuli, these data suggest that a specialized region in the NST is preferentially involved in processing a common aspect of bitter tastants. In contrast to citric acid, quinine, denatonium and propylthiouracil all elicited vigorous oromotor rejection responses, consistent with our earlier hypothesis that the medial third of the NST may be an afferent trigger zone for oromotor rejection.

Animals↗

Microsomal triglyceride transfer protein gene expression and ApoB secretion are inhibited by bitter melon in HepG2 cells.

Momordica charantia or bitter melon is traditionally used as an antidiabetic agent in Asia, Africa, and South America. Recent studies indicate that bitter melon can also lower plasma lipids and VLDL in diabetic animal models as well as animals fed a high-fat diet, suggesting an effect on lipoprotein metabolism. The aim of this study was to delineate the cellular and molecular mechanisms involved in the lipid-lowering properties of bitter melon and regulation of apolipoprotein B (apoB). Human hepatoma cells, HepG2, treated with bitter melon juice (BMJ) for 24 h reduced apoB secretion with and without the addition of lipids (P < 0.05). However, BMJ did not increase apoB secretion in cells treated with N-acetyl-leucyl-leucyl-norleucinal, indicating a lack of effect on the proteasomal degradation pathway. BMJ reduced the secretion of new triglycerides (P < 0.05) and decreased microsomal triglyceride transfer protein (MTP) mRNA expression, suggesting that lipid bioavailability and lipidation of lipoprotein assembly are likely involved in decreased apoB secretion. Interestingly, BMJ increased the nuclear translocation of the mature form of sterol regulatory element-binding protein-1c (SREBP-1c, P < 0.05), involved in MTP secretion. Our data suggest that BMJ is a potent inhibitor of apoB secretion and TG synthesis and secretion that may be involved in the plasma lipid- and VLDL-lowering effects observed in animal studies.

Apolipoproteins B↗

Impact of bitter taste on gastric motility.

BACKGROUND: Unexplained nausea and vomiting is often associated with delayed gastric emptying in patients with functional dyspepsia. We hypothesized that the experience of an unpleasant, nauseating taste could lead to a delay in gastric emptying. METHODS: Sixteen healthy women consumed a bland liquid test meal on three separate study days. On two of the study days subjects sham fed either a bitter tasting, modified Slim-Fast bar or one with a pleasant strawberry flavour. The time for 50% gastric emptying (GE(50)) was non-invasively assessed by electrical impedance tomography and antral motility by electrogastrography (EGG). RESULTS: Gastric emptying was significantly delayed by sham feeding the bitter compared with the pleasant bar, GE(50) 24.7+/-3.9 versus 17.2+/-1.8 min, P<0.05. EGG power rose significantly during both the pleasant (basal 1.46+/-0.07 to 2.33+/-0.14 log(10) microV(2)/min, P=0.000) and the bitter sham feed (basal 1.64+/-0.09 to 2.35+/-0.11 log(10) microV(2)/min, P=0.000). CONCLUSION: An unpleasant bitter taste delays gastric emptying but does not significantly impair antral motility.

Adult↗

Genetic tracing shows segregation of taste neuronal circuitries for bitter and sweet.

The recent discovery of mammalian bitter, sweet, and umami taste receptors indicates how the different taste qualities are encoded at the periphery. However, taste representations in the brain remain elusive. We used a genetic approach to visualize the neuronal circuitries of bitter and sweet tastes in mice to gain insight into how taste recognition is accomplished in the brain. By selectively expressing a transsynaptic tracer in either bitter- or sweet and/or umami-responsive taste receptor cells, and by comparing the locations of the tracer-labeled neurons in the brain, our data revealed the potential neuronal bases that underlie discrimination of bitter versus sweet.

Animals↗

Effect of liu-junzi-tang on the symptom of bitter taste in patients with chronic gastritis.

A symptom of bitter taste was found in 15 out of 82 patients with chronic gastritis that was diagnosed from symptoms and endoscopic findings. Liu-junzi-tang was very effective in 12 (80%) of the 15 patients. The symptom of bitter taste completely disappeared in 24.7 days on average after oral administration of Liu-junzi-tang in these 12 patients. In the remaining 3 patients, the symptom of bitter taste did not completely disappear, but was improved. Other symptoms associated with chronic gastritis and endoscopic findings were also improved in these patients. These findings indicate that Liu-junzi-tang may be a good remedy for the symptom of bitter taste in patients with chronic gastritis.

Adult↗

Possible novel mechanism for bitter taste mediated through cGMP.

Taste is the least understood among sensory systems, and bitter taste mechanisms pose a special challenge because they are elicited by a large variety of compounds. We studied bitter taste signal transduction with the quench-flow method and monitored the rapid kinetics of the second messenger guanosine 3',5'-cyclic monophosphate (cGMP) production and degradation in mouse taste tissue. In response to the bitter stimulants, caffeine and theophylline but not strychnine or denatonium cGMP levels demonstrated a rapid and transient increase that peaked at 50 ms and gradually declined throughout the following 4.5 s. The theophylline- and caffeine-induced effect was rapid, transient, concentration dependent and gustatory tissue-specific. The effect could be partially suppressed in the presence of the soluble guanylyl cyclase (GC) inhibitor 10 microM ODQ and 30 microM methylene blue but not 50 microM LY 83583 and boosted by nitric oxide donors 25 microM NOR-3 or 100 microM sodium nitroprusside. The proposed mechanism for this novel cGMP-mediated bitter taste signal transduction is cGMP production partially by the soluble GC and caffeine-induced inhibition of one or several phosphodiesterases.

Aminoquinolines↗

Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat.

Mammalian type 2 taste receptors (T2R) are a family of G protein-coupled receptors that mediate bitter signals in taste cells. In the present study, we compared the genomic organization of rodent T2R genes based on the recently completed mouse and rat genomes and examined tissue- and cell-specific expression of T2Rs. Both mouse and rat T2R families consist of 36 intact genes and at least 7 pseudogenes that are mapped to mouse chromosomes 15, 2, and 6 and to rat chromosomes 2, 3, and 4, respectively. All but two T2R genes are clustered on mouse chromosome 6 and rat chromosome 4 with virtually identical genomic organization. The orthologs of the first human T2R gene identified, mT2R119 and rT2R1, are located on mouse chromosome 15 and rat chromosome 2, whereas the novel rodent-specific T2R genes, mT2R134 and rT2R34, are located on mouse chromosome 2 and rat chromosome 3, respectively. Our results, using RT-PCR, demonstrate the presence of transcripts corresponding to the putative denatonium benzoate (DB) and phenylthiocarbamide (PTC) receptors in the antrum, fundus, and duodenum as well as in STC-1 and AR42J cells. The novel rodent-specific T2R gene (mT2R134 and rT2R34) was also expressed in these tissues and cell lines. The addition of DB, PTC, or cycloheximide to AR42J cells induced a rapid increase in the intracellular Ca(2+) concentration. The specificity of these effects is shown by the fact that these bitter stimuli did not induce any detectable Ca(2+) signaling in many other rodent or human cells that do not express receptors or G proteins implicated in bitter taste signaling. These results demonstrate that mouse and rat T2R genes are highly conserved in terms of genomic organization and tissue expression, suggesting that rodent T2Rs are evolved under similar dietary pressure and share bitter sensing functions in the lingual and gastrointestinal systems.

Animals↗