The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey

Background

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers.

Results

We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers.

Conclusion

In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.     

RELATIONSHIPS BETWEEN BITTER TASTE SENSITIVITY AND CONSUMPTION OF BITTER SUBSTANCES

The effect of consumption of bitter taste substances (caffeine and beer) to bitter taste sensitivity was examined by 19 healthy adults. For individual taste sensitivity, detection thresholds were used on 6 bitter substances (caffeine, iso-alpha-acids: beer bittering agents, quinine sulfate, L-tryptophan, L-phenylalanine and glycyl-L-phenylalanyl-L-phenylalanine) and 3 non-bitter substances (L-aspartic acid, aspartame and NaCl). Nonusers of caffeine had significantly higher sensitivity (lower threshold) for caffeine compared to moderate and heavy users. Slight consumers of beer had significantly higher sensitivity for iso-alpha-acids relative to heavy users of beer, Iso-alpha-acids were not detected in saliva in acute dosing test by using 6 subjects. The correlations between thresholds of 6 bitter substances were calculated. Significant correlations (p < 0.01) were noted in 2 cases between caffeine and quinine, and iso-alpha-acids and L-trypothan. These data suggest the significant relation between individual bitter taste sensitivity and the consumption of caffeine and beer (iso-alpha-acids).     

A psychophysical investigation of binary bitter-compound interactions

The aim of this study was to determine if taste interactions occur when bitter stimuli are mixed. Eight bitter stimuli were employed: denatonium benzoate (DB), quinine-HCl (QHCl), sucrose octaacetate (SOA), urea, L-tryptophan (L-trp), L-phenylalanine (L-phe), ranitidine-HCl, and Tetralone. The first experiment constructed individual psychophysical curves for each subject (n = 19) for each compound to account for individual differences in sensitivities when presenting bitter compounds in experiment 2. Correlation analysis revealed two groupings of bitter compounds at low intensity (1, L-trp, L-phe, and ranitidine; 2, SOA and QHCl), but the correlations within each group decreased as the perceived intensity increased. In experiment 2, intensity ratings and two-alternative forced-choice discrimination tasks showed that bitter compounds generally combine additively in mixture and do not show interactions with a few specific exceptions. The methods employed detected synergy among sweeteners, but could not detect synergy among these eight bitter compounds. In general, the perceived bitterness of these binary bitter-compound mixtures was an additive function of the total bitter-inducing stimuli in the mouth.     

EVIDENCE OF AN ADSORPTION-DESORPTION MODEL FOR HUMAN IRRITANT PERCEPTION

The temporal irritant response was evaluated for six concentrations of capsaicin, cinnamaldehyde, andpiperine, using time-intensity (TI) methodology. TI curves were evaluated using six TI parameters: maximum intensity (I_max), time-to-maximum (T_max), plateau time (T_plat), total time (T_tot), maximum rate of onset (M_onset) and maximum rate of decay (M_decay) of perception. Maximum intensity was used to evaluate the appropriateness of the Beidler taste equation, calculate the degree of affinity of the stimuli for the receptor (K_b), Gibbs free energy values, and the other TI parameter were used to quantify the adsorption desorptionprocesses. For cinnamaldehyde and capsaicin, correlation coefficients for the proposed Beidler taste model were 0.999, and 0.996, respectively. The large association constants (K_b) for cinnamaldehyde (25 M₋₁) and capsaicin (5.2 × 10⁴ M₋₁), compared to taste compounds, were consistent with their steep psychophysical functions and their persistent aftertastes. Concentration dependencies of T_max T_plat, T_tot, M_onset and M_decay, fit linear and semi-hyperbolic functions and were congruous with the proposed adsorption- desorption model for irritant perception.     

Sweet taste involves several distinct receptor mechanisms

Measures of human sensitivities to various sweet compounds conductedat threshold (91 subjects, 7 sweeteners) and at suprathresholdlevels (9 subjects, 12 sweeteners) show interindividual differences.Multidimensional analysis indicates that sweet taste can berepresented in a tridimensional continuum if 12 compounds areconsidered. Results are speculatively interpreted as indirectevidence for the existence of several receptor sites cooperatingin sweet taste chemoreception.     

Whole nerve chorda tympani responses to sweeteners in C57BL/6ByJ and 129P3/J mice

The C57BL/6ByJ (B6) strain of mice exhibits higher preferences than does the 129P3/J (129) strain for a variety of sweet tasting compounds. We measured gustatory afferent responses of the whole chorda tympani nerve in these two strains using a broad array of sweeteners and other taste stimuli. Neural responses were greater in B6 than in 129 mice to the sugars sucrose and maltose, the polyol D-sorbitol and the non-caloric sweeteners Na saccharin, acesulfame-K, SC-45647 and sucralose. Lower neural response thresholds were also observed in the B6 strain for most of these stimuli. The strains did not differ in their neural responses to amino acids that are thought to taste sweet to mice, with the exception of L-proline, which evoked larger responses in the B6 strain. Aspartame and thaumatin, which taste sweet to humans but are not strongly preferred by B6 or 129 mice, did not evoke neural responses that exceeded threshold in either strain. The strains generally did not differ in their neural responses to NaCl, quinine and HCl. Thus, variation between the B6 and 129 strains in the peripheral gustatory system may contribute to differences in their consumption of many sweeteners.     

The taste, odor and hedonic quality of polyglycerols

Twenty subjects judged the taste and odor intensity and thetaste and odor pleasantness/unpleasantness of five concentrationsof sucrose, glycerol, a commercial triglycerol, a syntheticlinear diglycerol and a synthetic linear triglycerol. Judgmentsof intensity were made using the method of magnitude estimation;judgments of pleasantness/unpleasantness were made using a graphicline scale. Only the two linear polyglycerols had appreciableodor intensity. Both were described as having an ‘acrid’or ‘burnt caramel’ quality. The odor exponent forthe linear triglycerol was extremely high (1.44) and may beattributed to its intensely unpleasant quality. Sucrose wascharacterized solely by sweet taste, glycerol and the commercialtriglycerol by sweet and bitter tastes, the linear diglycerolby sweet, bitter and sour tastes, and the linear triglycerolby bitter and sour tastes. The relationships between perceivedtaste intensity and concentration were well described by powerfunctions, although the slope of the psychophysical functionfor the linear triglycerol was markedly lower than that forthe other compounds. The relative order of taste intensitieswas: linear triglycerol > sucrose > glycerol = lineardiglycerol > commercial triglycerol. Judgments of taste (andodor) pleasantness/unpleasantness showed only sucrose and glycerolto have positive hedonic qualities. All the polyglycerols werejudged unpleasant at all concentrations. Differences in thetaste and odor characteristics of the commercial and synthetictriglycerols were attributed to the commercial product beinga mixture of over 20 compounds. Although the synthetic lineardi- and triglycerols are effective in lowering water activity,these data suggest that more purified crystalline forms mustbe synthesized before they can be used effectively as humectantsfor intermediate moisture foods.     

Reduction of saltiness and bitterness after a chlorhexidine rinse

Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute chlorhexidine on taste has not been investigated. The purpose of the present study was to examine the effect of acute chlorhexidine rinses on taste intensity and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All stimuli were first matched for overall intensity so the effects of chlorhexidine would be directly comparable across compounds. As a control treatment, the bitter taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects participated in four experimental conditions: a pre-test, a quinine treatment, a chlorhexidine treatment, and a post-test condition, while rating total taste intensity and taste qualities in separate test sessions. Relative to the quinine treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and NH4Cl, and not to significantly affect the tastes of sucrose, monosodium glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses relative to water rinses, but were only marginally suppressed relative to quinine rinses. Potential mechanisms are discussed.     

Changes in Taste Perception Following Mental or Physical Stress

Taste perception depends not only on the chemical and physicalproperties of tastants, but may also depend on the physiologicaland psychological conditions of those who do the tasting. Inthis study, the effects of mood state on taste sensitive wasevaluated in humans who were exposed to conditions of mentalor physical fatigue and tension. Taste responses to quininesulfate (bitter), citric acid (sour) and sucrose (sweet) weretested. The intensity of the taste sensations were recordedby a computerized time-intensity (TI) on-line system. Subjectsperformed mental tasks by personal computer or physical tasksby ergometer for 10–40 min. Before and after these sessions,the duration of the after-taste and the intensity of the sensationof taste were recorded by the TI system, and in addition, psychologicalmood states were evaluated with POMS (Profile of Mood State).TI evaluation showed that after the mental tasks, the perceivedduration of bitter, sour and sweet taste sensations was shortenedrelative to the control. Total amount of bitterness, sournessand sweetness was also significantly reduced. Furthermore, themaximum intensity of bitterness was significantly reduced. Therewere no significant differences in bitterness and sweetnesssensations following physical tasks. However, relative to beforethe physical task, the duration of the after-taste of sournesswas significantly shortened by the physical task. After thephysical task, the buffering capacity of saliva was significantlyincreased. Thus mental and physical tasks alter taste perceptionin different ways; the mechanisms underlying these changes remainto be determined. Chem. Senses 21: 195–200, 1996.     

Drosophila melanogaster prefers compounds perceived sweet by humans

To understand the functional similarities of fly and mammalian taste receptors, we used a top-down approach that first established the fly sweetener-response profile. We employed the fruit fly Drosophila melanogaster, an omnivorous human commensal, and determined its sensitivity to an extended set of stimuli that humans find sweet. Flies were tested with all sweeteners in 2 assays that measured their taste reactivity (proboscis extension assay) and their ingestive preferences (free roaming ingestion choice test). A total of 21 sweeteners, comprised of 11 high-potency sweeteners, 2 amino acids, 5 sugars, 2 sugar alcohols, and a sweet salt (PbCl2), were tested in both assays. We found that wild-type Drosophila responded appetitively to most high-potency sweeteners preferred by humans, even those not considered sweet by rodents or new world monkeys. The similarities in taste preferences for sweeteners suggest that frugivorous/omnivorous apes and flies have evolved promiscuous carbohydrate taste detectors with similar affinities for myriad high-potency sweeteners. Whether these perceptual parallels are the result of convergent evolution of saccharide receptor-binding mechanisms remains to be determined.     

Coding of sweet,bitter, and umami tastes: different receptor cells sharing similar signaling pathways

Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.     

Riboflavin-binding protein is a novel bitter inhibitor

Riboflavin-binding protein (RBP) from chicken egg, which was recently reported to be a selective sweet inhibitor for protein sweeteners, was also found to be a bitter inhibitor. RBP elicited broadly tuned inhibition of various bitter substances including quinine-HCl, naringin, theobromine, caffeine, glycyl-L-phenylalanine (Gly-Phe), and denatonium benzoate, whereas several other proteins, such as ovalbumin (OVA) and beta-lactoglobulin, were ineffective in reducing bitterness of these same compounds. Both the bitter tastes of quinine and caffeine were reduced following an oral prerinse with RBP. It was found that RBP binds to quinine but not to caffeine, theobromine, naringin, and Gly-Phe. However, the binding of RBP to quinine was probably not responsible for the bitter inhibition because OVA bound to quinine as well as RBP. Based on these results, it is suggested that the bitter inhibitory effect of RBP is the consequence of its ability to interact with taste receptors rather than because it interacts with the bitter tastants themselves. RBP may have practical uses in reducing bitterness of foods and pharmaceuticals. It may also prove a useful tool in studies of mechanisms of bitter taste.     

POTENCY OF SWEETNESS OF ASPARTAME, D-TRYPTOPHAN AND THAUMATIN EVALUATED BY SINGLE VALUE AND TIME-INTENSITY MEASUREMENTS

Perceived sweetness of sucrose, aspartame, D-tryptophan and thaumatin in a sour, citric acid background was analyzed in terms of the potency of these compounds relative to sucrose-water combinations. Potencies of the sweeteners were determined from (1) maximum intensity using single value and time-intensity (T-I) measurements and (2) average intensity calculated as the ratio of area under the T-I curve and total perceived time. Stevens' law was applied to sweet responses, either in static or dynamic conditions. It was found that the exponent of the concentration-response function reflected the relative capacity of a compound to sweeten a given food and stressed differences of potency among sweeteners. Aspartame, D-tryptophan and thaumatin exhibited a decrease in sweetness potency relative to sucrose as sweetness increased from 10 to 100% of the full scale of response. Across the entire sweetness range, thaumatin showed the greatest potency but its long persistence time led to differentiate this intense sweetener from the other sweeteners evaluated.     

Effects of linoleic acid on sweet, sour, salty, and bitter taste thresholds and intensity ratings of adults

Evidence supporting a taste component for dietary fat has prompted study of plausible transduction mechanisms. One hypothesizes that long-chain, unsaturated fatty acids block selected delayed-rectifying potassium channels, resulting in a sensitization of taste receptor cells to stimulation by other taste compounds. This was tested in 17 male and 17 female adult (mean +/- SE age = 23.4 +/- 0.7 yr) propylthiouracil tasters with normal resting triglyceride concentrations (87.3 +/- 5.6 mg/day) and body mass index (23.3 +/- 0.4 kg/m(2)). Participants were tested during two approximately 30-min test sessions per week for 8 wk. Eight stimuli were assessed in duplicate via an ascending, three-alternative, forced-choice procedure. Qualities were randomized over weeks. Stimuli were presented as room-temperature, 5-ml portions. They included 1% solutions of linoleic acid with added sodium chloride (salty), sucrose (sweet), citric acid (sour), and caffeine (bitter) as well as solutions of these taste compounds alone. Participants also rated the intensity of the five strongest concentrations using the general labeled magnitude scale. The suprathreshold samples were presented in random order with a rinse between each. Subjects made the ratings self-paced while wearing nose clips. It was hypothesized that taste thresholds would be lower and absolute intensity ratings or slopes of intensity functions would be higher for the stimuli mixed with the linoleic acid. Thresholds were compared by paired t-tests and intensity ratings by repeated measures analysis of variance. Thresholds were significantly higher (i.e., lower sensitivity) for the sodium chloride, citric acid, and caffeine solutions with added fatty acid. Sweet, sour, and salty intensity ratings were lower or unchanged by the addition of a fatty acid. The two highest concentrations of caffeine were rated as weaker in the presence of linoleic acid. These data do not support a mechanism for detecting dietary fats whereby fatty acids sensitize taste receptor cells to stimulation by taste compounds.     

Modulation of Sweet Taste by Umami Compounds via Sweet Taste Receptor Subunit hT1R2

Although the five basic taste qualities—sweet, sour, bitter, salty and umami—can be recognized by the respective gustatory system, interactions between these taste qualities are often experienced when food is consumed. Specifically, the umami taste has been investigated in terms of whether it enhances or reduces the other taste modalities. These studies, however, are based on individual perception and not on a molecular level. In this study we investigated umami-sweet taste interactions using umami compounds including monosodium glutamate (MSG), 5’-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu) and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3-expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly attenuated by MSG and umami active peptides but not by umami active nucleotides. Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious when sweet receptors are activated by sweeteners that target the extracellular domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate, which interact with the T1R3 transmembrane domain (TMD). Application of umami compounds with lactisole, inhibitory drugs that target T1R3, exerted a more severe inhibitory effect. The inhibition was also observed with F778A sweet receptor mutant, which have the defect in function of T1R3 TMD. These results suggest that umami peptides affect sweet taste receptors and this interaction prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric manner, not to the T1R3. This is the first report to define the interaction between umami and sweet taste receptors.     

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-niethoxyphenoxy)propanoicacid (sodium gait) (Na-PMP) on the taste and temporal propertiesof a range of bitter-sweet stimuli was determined using a trainedsensory panel. Na-PMP was found to be an effective inhibitorof the sweetness response of all stimuli tested, reducing bothsweetness intensity and persistence. The inhibitor was foundto be specific to sweet taste, no reduction in bitterness intensityor persistence was observed at the concentrations of Na-PMPemployed in this study. The results therefore do not supportthe claim of Fuller and Kurtz (1991), that Na-PMP is a potentbitterness inhibitor, but rather support the existence of twodistinct receptor sites/loci in sweet and bitter chemoreception.     

Sweet and bitter tastants specific detection by the taste cell-based sensor

Sweet and bitter tastants specific detection by cell-based sensor is investigated in this paper. Human enteroendocrine NCI-H716 cells, expressing G protein-coupled receptors and sweet receptors (type 1, member 2/type 1, member 3), and human enteroendocrine STC-1 cells, expressing G protein-coupled receptors and bitter receptors (type 2 members) are used as sensing devices. The HEK-293 cells, without taste receptor expression, are used as negative control. The electrochemical impedance spectrum data is recorded and processed by bistable stochastic resonance for signal-to-noise ratio calculation. NCI-H716 cell-based sensor selectively responds to sweeteners and sweet tastant mixtures. STC-1 cell-based sensor selectively responds to bitter tastants and bitter tastant mixtures. The tastants species and concentrations can be decided by signal-to-noise ratio parameters. HEK-293 cell-based sensor lacks the tastants discriminating ability. The taste cell-based sensor is easy to prepare and operate. This work offers a useful way in gustatory mechanism research.     

Intensity/time relationships in sweetness: evidence for a queue hypothesis in taste chemoreception

Details of reaction time, total persistence time and time ofprotracted maximum intensity of sweetness in relation to concentrationof sucrose and thaumatin are presented. Reaction time approachesa constant value at an early concentration for both sweetenersand maximum times for maximum intensity occur at lower concentrationsthan total maximum persistence. These observations seem bestexplained by a two-stage model of taste chemoreception, thefirst consisting of an orderly queue of stimulus molecules approachingthe ionophor and the second being the depolarisation at theionophor itself. The orderly queue model is capable of explainingall the temporal phenomena of sweet taste including the plateauof maximum time at maximum intensity which is observed at allconcentrations. It also offers a novel view of the way in whichintense sweeteners such as thaumatin may achieve their effectsand broadens the scope for taste modifier research in the future.     

棉铃虫幼虫对人类呈味物质的取食反应

利用叶碟法在室内测定了棉铃虫对人类酸、甜、苦、咸4种基本呈味物质和麻、辣味2种植物提取物的取食反应。正交试验结果表明,棉铃虫幼虫对用甜味、苦味和辣味物质(蔗糖、奎宁和辣椒提取物)处理过的烟叶取食选择率较高,对这3种呈味物质表现出有较好的适应性;而幼虫对咸味、酸味和麻味物质(氯化钠、柠檬酸和花椒提取物)处理过的烟叶取食量较少,这3种呈味物质表现出较强的拒食活性。在选择性条件下,幼虫的取食量与花椒提取物剂量显著相关;而在非选择性条件下,幼虫的取食量与氯化钠剂量显著相关。