Sweet Taste Perception Research Articles

Amiloride reduces the sweet taste intensity by inhibiting the human sweet taste receptor

In mammals, sweet taste perception is mediated by the heterodimeric G-protein-coupled receptor, T1R2/T1R3. An interesting characteristic of this sweet taste receptor is that it has multiple ligand binding sites. Although there have been several studies on agonists of sweet taste receptors, little is known about antagonists of these receptors. In this study, we constructed a cell line stably expressing the human sweet taste receptor (hT1R2/hT1R3) and a functional chimeric G-protein (hGα16gust44) using the Flp-In system for measuring the antagonistic activity against the receptor. This constructed cell line responded quite intensely and frequently to the compounds applied for activation of hT1R2/hT1R3. In the presence of 3mM amiloride, the responses to sweet tastants such as sugar, artificial sweetener, and sweet protein were significantly reduced. The inhibitory activity of amiloride toward 1mM aspartame was observed in a dose-dependent manner with an IC50 value of 0.87mM. Our analysis of a cell line expressing hT1R3 mutants (hT1R3-A733V or hT1R3-F778A) made us to conclude that the target site of amiloride is distinct from that of lactisole, a known sweet taste inhibitor. Our results strongly indicate that amiloride reduces the sweet taste intensity by inhibiting the human sweet taste receptor and also that this receptor has multiple inhibitor binding sites.

Obese Women Have Lower Monosodium Glutamate Taste Sensitivity and Prefer Higher Concentrations Than Do Normal‐weight Women

The goal of this study was to determine whether obese women exhibit altered umami and sweet taste perception compared to normal-weight women. A total of 57 subjects (23 obese and 34 normal weight) participated in a 2-day study separated by 1 week. Half of the women in each group were evaluated using monosodium glutamate (MSG; prototypical umami stimulus) on the first test day and sucrose on the second test day; the order was reversed for the remaining women. We used two-alternative forced-choice staircase procedures to measure taste detection thresholds, forced-choice tracking technique to measure preferences, the general Labeled Magnitude Scale (gLMS) to measure perceived intensity of suprathreshold concentrations, and a triangle test to measure discrimination between 29 mmol/l MSG and 29 mmol/l NaCl. Obese women required higher MSG concentrations to detect a taste and preferred significantly higher MSG concentrations in a soup-like vehicle. However, their perception of MSG at suprathreshold concentrations, their ability to discriminate MSG from salt, and their preference for sucrose were similar to that observed in normal-weight women. Regardless of their body weight category, 28% of the women did not discriminate 29 mmol/l MSG from 29 mmol/l NaCl (nondiscriminators). Surprisingly, we found that, relative to discriminators, nondiscriminators perceived less savoriness when tasting suprathreshold MSG concentrations and less sweetness from suprathreshold sucrose concentrations but had similar MSG and sucrose detection thresholds. Taken together, these data suggest that body weight is related to some components of umami taste and that different mechanisms are involved in the perception of threshold and suprathreshold MSG concentrations.

Nutritional status alters saccharin intake and sweet receptor mRNA expression in rat taste buds

Sweet taste usually signifies the presence of caloric food. It is commonly accepted that a close association exists among sweet taste perception, preference, and nutritional status. However, the mechanisms involved remain unknown. To investigate whether nutritional status affects the preference for palatable solutions and alters sweet taste receptor gene expression in rats, we measured saccharin intake and preference using a two-bottle preference test, and changes in body weight, plasma leptin levels, and gene expression for the sweet taste receptor in taste buds in high-fat diet-induced obese rats and chronically diet-restricted rats. We found that the consumption and preference ratios for 0.01 and 0.04 M saccharin were significantly lower in the high-fat diet-induced obese rats than in the normal diet rats, while the serum leptin levels were markedly increased in obese rats. Consistent with the changes in saccharin intake, the gene expression level of the sweet taste receptor T1R3 was significantly decreased in the high-fat diet-induced obese rats compared with the control rats. By contrast, the chronically diet-restricted rats showed remarkably enhanced consumption and preference for 0.04 M saccharin. The serum leptin concentration was decreased, and the gene expression of the leptin receptor was markedly increased in the taste buds. In conclusion, our results suggest that nutritional status alters saccharin preference and the expression of T1R3 in taste buds. These processes may be involved in the mechanisms underlying the modulation of peripheral sweet taste sensitivity, in which leptin plays a role.

Influence of Prolonged Exercise on Sweet Taste Perception

Abstract: In order to determine the influence of prolonged exercise on sensitivity to sweet taste, we investigated the relationship between physical fatigue and palatability and/or taste intensity by performing sensory evaluation tests. The subjects hiked up a 36-km mountain trail for 12 h, and we used 100- and 300-mM sucrose solutions as test samples. The taste intensity and palatability of the sucrose solutions did not change significantly during exercise. However, a slight change in palatability was observed. In particular, the palatability of the 300-mM solution increased with an increase in the degree of physical fatigue towards the end of the exercise.

Modulation and Transmission of Sweet Taste Information for Energy Homeostasis

Perception of sweet taste is important for animals to detect external energy source of calories. In mice, sweet-sensitive cells possess a leptin receptor. Increase of plasma leptin with increasing internal energy storage in the adipose tissue suppresses sweet taste responses via this receptor. Data from our recent studies indicate that leptin may also modulate sweet taste sensation in humans with a diurnal variation in sweet sensitivity. This leptin modulation of sweet taste information to the brain may influence individuals' preference and ingestive behavior, thereby playing important roles in regulation of energy homeostasis.

Allelic Polymorphism within the TAS1R3 Promoter Is Associated with Human Taste Sensitivity to Sucrose

Human sweet taste perception is mediated by the heterodimeric G protein-coupled receptor encoded by the TAS1R2 and TAS1R3 genes. Variation in these genes has been characterized, but the functional consequences of such variation for sweet perception are unknown. We found that two C/T single-nucleotide polymorphisms (SNPs) located at positions -1572 (rs307355) and -1266 (rs35744813) upstream of the TAS1R3 coding sequence strongly correlate with human taste sensitivity to sucrose and explain 16% of population variability in perception. By using a luciferase reporter assay, we demonstrated that the T allele of each SNP results in reduced promoter activity in comparison to the C alleles, consistent with the phenotype observed in humans carrying T alleles. We also found that the distal region of the TAS1R3 promoter harbors a composite cis-acting element that has a strong silencing effect on promoter activity. We conclude that the rs307355 and rs35744813 SNPs affect gene transcription by altering the function of this regulatory element. A worldwide population survey reveals that the T alleles of rs307355 and rs35744813 occur at lowest frequencies in European populations. We propose that inherited differences in TAS1R3 transcription account for a substantial fraction of worldwide differences in human sweet taste perception.

Time-Intensity Studies of Sweeteners

We used time-intensity studies in this work for evaluating the perception of sweet taste of sucralose, aspartame, and saccharose over time. In second part of this study the mixture of sweeteners and zinc sulphate, which modifies sweet taste perception, was used. We determined the following parameters from the assessor’s charts of time profile: maximum intensity of sweet taste and the time which was needed to get to its maximum, the time period of perception of sweet taste and the area under the curve. For evaluation each assessor received 20 ml of a water solution with the sweetener followed by the mixture of the same sweetener with zinc sulphate. The intensity of sweet taste was measured before and after spitting out the solution. Then it was measured at intervals of 5 s for 70 seconds. It can be seen from the charts that sucralose has a more gentle sweet taste perception in time than the other sweeteners and that the zinc sulphate modifies the sweet taste but it does not inhibit it absolutely.

Identification of tactile mechanisms for the evaluation of object sizes during texture perception

Perception of sour, sweet, bitter, and salty taste can be related to specialized sensors (taste buds), however, this is not possible for texture perception. Although different types of oral mechanoreceptors are known, it remains unclear how texture perception relates to these structures. The aim of this work is to better understand textural attributes such as grittiness. As a first step to this end, an experimental determination of size resolution capability was carried out. Small discs of varying diameter, thickness, and materials were evaluated by subjects for differences in diameter and thickness between tongue and palate (oral system) and also between finger and palm (manual system). Diameter determination was found to be very accurate. Thickness evaluation was more complex and appeared to rely on two mechanisms. Differences between the manual and oral evaluation were found and could be explained in terms of mechanical models as well as anatomical data. The hypothesis of two different mechanisms was experimentally verified.

Genetic Variation in Taste and Its Influence on Food Selection

Abstract Taste perception plays a key role in determining individual food preferences and dietary habits. Individual differences in bitter, sweet, umami, sour, or salty taste perception may influence dietary habits, affecting nutritional status and nutrition-related chronic disease risk. In addition to these traditional taste modalities there is growing evidence that "fat taste" may represent a sixth modality. Several taste receptors have been identified within taste cell membranes on the surface of the tongue, and they include the T2R family of bitter taste receptors, the T1R receptors associated with sweet and umami taste perception, the ion channels PKD1L3 and PKD2L1 linked to sour taste, and the integral membrane protein CD36, which is a putative "fat taste" receptor. Additionally, epithelial sodium channels and a vanilloid receptor, TRPV1, may account for salty taste perception. Common polymorphisms in genes involved in taste perception may account for some of the interindividual differences in food preferences and dietary habits within and between populations. This variability could affect food choices and dietary habits, which may influence nutritional and health status and the risk of chronic disease. This review will summarize the present state of knowledge of the genetic variation in taste, and how such variation might influence food intake behaviors.

The capsaicin receptor participates in artificial sweetener aversion

Artificial sweeteners such as saccharin, aspartame, acesulfame-K, and cyclamate produce at high concentrations an unpleasant after-taste that is generally attributed to bitter and metallic taste sensations. To identify receptors involved with the complex perception of the above compounds, preference tests were performed in wild-type mice and mice lacking the TRPV1 channel or the T1R3 receptor, the latter being necessary for the perception of sweet taste. The sweeteners, including cyclamate, displayed a biphasic response profile, with the T1R3 mediated component implicated in preference. At high concentrations imparting off-taste, omission of TRPV1 reduced aversion. In a heterologous expression system the Y511A point mutation in the vanilloid pocket of TRPV1 did not affect saccharin and aspartame responses but abolished cyclamate and acesulfame-K activities. The results rationalize artificial sweetener tastes and off-tastes by showing that at low concentrations, these molecules stimulate the gustatory system through the hedonically positive T1R3 pathway, and at higher concentrations, their aversion is partly mediated by TRPV1.

Abnormal Taste Perception in Mice Lacking the Type 3 Inositol 1,4,5-Trisphosphate Receptor

Inositol 1,4,5-trisphosphate receptor (IP3R) is one of the important calcium channels expressed in the endoplasmic reticulum and has been shown to play crucial roles in various physiological phenomena. Type 3 IP3R is expressed in taste cells, but the physiological relevance of this receptor in taste perception in vivo is still unknown. Here, we show that mice lacking IP3R3 show abnormal behavioral and electrophysiological responses to sweet, umami, and bitter substances that trigger G-protein-coupled receptor activation. In contrast, responses to salty and acid tastes are largely normal in the mutant mice. We conclude that IP3R3 is a principal mediator of sweet, bitter, and umami taste perception and would be a missing molecule linking phospholipase C beta2 to TRPM5 activation.

Effects of Cigarette Smoking and Family History of Alcoholism on Sweet Taste Perception and Food Cravings in Women

Despite popular beliefs that smoking affects the sensitivity and liking of sweet-tasting foods and beverages, few psychophysical studies have examined this phenomenon and none have taken into account the individual's family history of alcoholism (FH+), a predictor of heightened sweet preferences. A within- and between-subjects study was conducted to determine the effect of both cigarette smoking and an acute exposure to nicotine on sweet taste sensitivity and preferences in women. Two groups were studied on 2 days separated by 1 week: women who were current smokers (n = 27, 18 were FH+) and those who never smoked in their lifetime (n = 22, 9 were FH+). Current smokers smoked nicotine-containing cigarettes during 1 test session and nicotine-free cigarettes during the other. The procedures were identical during both test sessions for the group of never smokers, with the exception that they did not smoke. Two-alternative staircase methods and forced-choice tracking procedures were used to assess sucrose thresholds and preferences, respectively, during both test session. Standardized questionnaires were administered to assess food cravings as well as smoking and alcohol usage and dependence. The Family Interview for Genetic Studies was used to detect alcoholism according to the DSM III criteria for family members up to second-degree relatives. Acute exposure to nicotine did not affect sucrose detection thresholds or preferences, but smokers had significantly higher sucrose detection thresholds than never smokers. The greater the smoking dose in pack-years, the lower the sucrose sensitivity. Regardless of smoking status, women who were FH+ preferred significantly higher sucrose concentrations and craved sweets more often than women who were not. Both smoking and having a family history of alcoholism had differential effects on sweet taste. Smoking was associated with decreased sweet taste sensitivity whereas having a family history of alcoholism was associated with heightened sweet preferences. These findings suggests that future research on the effects of smoking on food habits and cravings should take into account family history of alcoholism given its association with sweet liking and the increased likelihood to develop a tobacco disorder.

The binding site for neohesperidin dihydrochalcone at the human sweet taste receptor

BackgroundDifferences in sweet taste perception among species depend on structural variations of the sweet taste receptor. The commercially used isovanillyl sweetener neohesperidin dihydrochalcone activates the human but not the rat sweet receptor TAS1R2+TAS1R3. Analysis of interspecies combinations and chimeras of rat and human TAS1R2+TAS1R3 suggested that the heptahelical domain of human TAS1R3 is crucial for the activation of the sweet receptor by neohesperidin dihydrochalcone.ResultsBy mutational analysis combined with functional studies and molecular modeling we identified a set of different amino acid residues within the heptahelical domain of human TAS1R3 that forms the neohesperidin dihydrochalcone binding pocket. Sixteen amino acid residues in the transmembrane domains 2 to 7 and one in the extracellular loop 2 of hTAS1R3 influenced the receptor's response to neohesperidin dihydrochalcone. Some of these seventeen residues are also part of the binding sites for the sweetener cyclamate or the sweet taste inhibitor lactisole. In line with this observation, lactisole inhibited activation of the sweet receptor by neohesperidin dihydrochalcone and cyclamate competitively, whereas receptor activation by aspartame, a sweetener known to bind to the N-terminal domain of TAS1R2, was allosterically inhibited. Seven of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are thought to play a role in the binding of allosteric modulators of other class C GPCRs, further supporting our model of the neohesperidin dihydrochalcone pharmacophore.ConclusionFrom our data we conclude that we identified the neohesperidin dihydrochalcone binding site at the human sweet taste receptor, which overlaps with those for the sweetener cyclamate and the sweet taste inhibitor lactisole. This readily delivers a molecular explanation of our finding that lactisole is a competitive inhibitor of the receptor activation by neohesperidin dihydrochalcone and cyclamate. Some of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are involved in the binding of allosteric modulators in other class C GPCRs, suggesting a general role of these amino acid positions in allosterism and pointing to a common architecture of the heptahelical domains of class C GPCRs.

Perception of sweet taste is important for voluntary alcohol consumption in mice.

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

The relationship between the perception of sweet and salty tastes and the addition of potato starch

The relationship between the perception of sweet and salty tastes and the addition of potato starch

Influence of temperature on taste perception.

Daily experience tells us that temperature has a strong influence on how we taste. Despite the longstanding interest of many specialists in this aspect of taste, we are only starting to understand the molecular mechanisms underlying the temperature dependence of different taste modalities. Recent research has led to the identification of some strong thermosensitive molecules in the taste transduction pathway. The cold activation of the epithelial Na(+) channel and the heat activation of the taste variant of the vanilloid receptor (TRPV1t) may underlie the temperature dependence of salt responses. Heat activation of the transient receptor potential channel TRPM5 explains the enhancement of sweet taste perception by warm temperatures. Current development of methods to study taste cell physiology will help to determine the contribution of other temperature-sensitive events in the taste transduction pathways. Vice versa, the analysis of the thermodynamic properties of these events may assist to unveil the nature of several taste processes.

The Human Sweet Tooth

Humans love the taste of sugar and the word "sweet" is used to describe not only this basic taste quality but also something that is desirable or pleasurable, e.g., la dolce vita. Although sugar or sweetened foods are generally among the most preferred choices, not everyone likes sugar, especially at high concentrations. The focus of my group's research is to understand why some people have a sweet tooth and others do not. We have used genetic and molecular techniques in humans, rats, mice, cats and primates to understand the origins of sweet taste perception. Our studies demonstrate that there are two sweet receptor genes (TAS1R2 and TAS1R3), and alleles of one of the two genes predict the avidity with which some mammals drink sweet solutions. We also find a relationship between sweet and bitter perception. Children who are genetically more sensitive to bitter compounds report that very sweet solutions are more pleasant and they prefer sweet carbonated beverages more than milk, relative to less bitter-sensitive peers. Overall, people differ in their ability to perceive the basic tastes, and particular constellations of genes and experience may drive some people, but not others, toward a caries-inducing sweet diet. Future studies will be designed to understand how a genetic preference for sweet food and drink might contribute to the development of dental caries.

Heat activation of TRPM5 underlies thermal sensitivity of sweet taste

TRPM5, a cation channel of the TRP superfamily, is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweet, umami and bitter tastes. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and is proposed to generate a depolarizing potential in the taste receptor cells. Factors that modulate TRPM5 activity are therefore expected to influence taste. Here we show that TRPM5 is a highly temperature-sensitive, heat-activated channel: inward TRPM5 currents increase steeply at temperatures between 15 and 35 degrees C. TRPM4, a close homologue of TRPM5, shows similar temperature sensitivity. Heat activation is due to a temperature-dependent shift of the activation curve, in analogy to other thermosensitive TRP channels. Moreover, we show that increasing temperature between 15 and 35 degrees C markedly enhances the gustatory nerve response to sweet compounds in wild-type but not in Trpm5 knockout mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans, including enhanced sweetness perception at high temperatures and 'thermal taste', the phenomenon whereby heating or cooling of the tongue evoke sensations of taste in the absence of tastants.

Objective Assessment of Terbinafine‐Induced Taste Loss

Terbinafine (Lamisil), a widely prescribed oral antifungal agent, reportedly induces taste loss in 0.6% to 2.8% of those taking the drug. However, many so-called taste problems reflect olfactory problems, and the sole empirical study published on this topic, based on whole-mouth testing of a single subject, found no terbinafine-related deficit. In this study, we quantitatively assessed, using well-validated taste and smell tests, chemosensory function in six patients complaining of taste disturbance after terbinafine treatment and compared their test scores to those of six age-, race-, and sex-matched normal controls. Taste function was measured using a 96-trial regional test that assesses sweet, sour, bitter, and salty taste perception within the anterior (cranial nerve [CN] VII) and posterior (CN IX) lingual taste bud fields. Smell function was bilaterally evaluated using the 40-item University of Pennsylvania Smell Identification Test. Taste function for sweet-, sour-, and bitter-tasting stimuli was significantly depressed in both the anterior and posterior lingual regions. For sodium chloride, the decrements were confined to the posterior region. Olfactory function was within normal limits. These findings 1) support anecdotal case reports of taste loss after terbinafine use, 2) demonstrate that all four major taste qualities are affected, and 3) suggest that olfactory dysfunction is not involved. Because self-report markedly underestimates chemosensory deficits, more extensive quantitative testing of patients receiving terbinafine will likely reveal a much higher prevalence of terbinafine-induced taste loss than currently reported. Since being older than 65 years of age and having a low body mass index are reportedly risk factors for terbinafine-induced taste loss, physicians should be particularly on the alert for elderly persons taking this medication who may become depressed or alter their food intake in response to decreased taste sensation.

Bitterness Suppression with Zinc Sulfate and Na-Cyclamate: A Model of Combined Peripheral and Central Neural Approaches to Flavor Modification

Zinc sulfate is known to inhibit the bitterness of the antimalarial agent quinine [R. S. J. Keast. The effect of zinc on human taste perception. J. Food Sci. 68:1871-1877 (2003)]. In the present work, we investigated whether zinc sulfate would inhibit other bitter-tasting compounds and pharmaceuticals. The utility of zinc as a general bitterness inhibitor is compromised, however, by the fact that it is also a good sweetness inhibitor [R. S. J. Keast, T. Canty, and P. A. S. Breslin. Oral zinc sulfate solutions inhibit sweet taste perception. Chem. Senses 29:513-521 (2004)] and would interfere with the taste of complex formulations. Yet, zinc sulfate does not inhibit the sweetener Na-cyclamate. Thus, we determined whether a mixture of zinc sulfate and Na-cyclamate would be a particularly effective combination for bitterness inhibition (Zn) and masking (cyclamate). We used human taste psychophysical procedures with chemical solutions to assess bitterness blocking. Zinc sulfate significantly inhibited the bitterness of quinine-HCl, Tetralone, and denatonium benzoate (DB) (p < 0.05), but had no significant effect on the bitterness of sucrose octa-acetate, pseudoephedrine (PSE), and dextromethorphan. A second experiment examined the influence of zinc sulfate on bittersweet mixtures. The bitter compounds were DB and PSE, and the sweeteners were sucrose (inhibited by 25 mM zinc sulfate) and Na-cyclamate (not inhibited by zinc sulfate). The combination of zinc sulfate and Na-cyclamate most effectively inhibited DB bitterness (86%) (p < 0.0016), whereas the mixture's inhibition of PSE bitterness was not different from that of Na-cyclamate alone. A combination of Na-cyclamate and zinc sulfate was most effective at inhibiting bitterness. Thus, the combined use of peripheral oral and central cognitive bitterness reduction strategies should be particularly effective for improving the flavor profile of bitter-tasting foods and pharmaceutical formulations.