Sweet Taste Stimuli Research Articles

Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (D-tryptophan, D-phenylalanine, L-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (L-glutamine, L-threonine, L-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5'-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system.

Taste Receptor Genes

In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity.

Signal transduction and information processing in mammalian taste buds

The molecular machinery for chemosensory transduction in taste buds has received considerable attention within the last decade. Consequently, we now know a great deal about sweet, bitter, and umami taste mechanisms and are gaining ground rapidly on salty and sour transduction. Sweet, bitter, and umami tastes are transduced by G-protein-coupled receptors. Salty taste may be transduced by epithelial Na channels similar to those found in renal tissues. Sour transduction appears to be initiated by intracellular acidification acting on acid-sensitive membrane proteins. Once a taste signal is generated in a taste cell, the subsequent steps involve secretion of neurotransmitters, including ATP and serotonin. It is now recognized that the cells responding to sweet, bitter, and umami taste stimuli do not possess synapses and instead secrete the neurotransmitter ATP via a novel mechanism not involving conventional vesicular exocytosis. ATP is believed to excite primary sensory afferent fibers that convey gustatory signals to the brain. In contrast, taste cells that do have synapses release serotonin in response to gustatory stimulation. The postsynaptic targets of serotonin have not yet been identified. Finally, ATP secreted from receptor cells also acts on neighboring taste cells to stimulate their release of serotonin. This suggests that there is important information processing and signal coding taking place in the mammalian taste bud after gustatory stimulation.

Taste perception and coding in the periphery.

Recent identification of taste receptors and their downstream signaling molecules, expressed in taste receptor cells, led to the understanding of taste coding in the periphery. Ion channels appear to mediate detection of salty and sour taste. The sensations of sweet, umami and bitter taste are initiated by the interaction of sapid molecules with the G-protein-coupled receptors T1Rs and T2Rs. Mice lacking either PLCbeta2 or TRPM5 diminish behavioral and nerve responses to sweet, umami and bitter taste stimuli, suggesting that both receptor families converge on a common signaling pathway in the taste receptor cells. Nevertheless, separate populations of taste cells appear to be uniquely tuned to sweet, umami and bitter taste. Since PLCbeta2-deficient mice still respond to sour and salty stimuli, sour and salty taste are perceived independent of bitter, umami and sweet taste. In this review, the recent characterization of the cellular mechanisms underlying taste reception and perception, and of taste coding in the periphery will be discussed.

Longitudinal study of taste identification of sensory panellists: Effect of Ageing, Experience and Exposure

It is generally known that training increases taste performance, but at the same time several studies reveal major taste impairment with age. In the present study, the influence of Ageing, Experience and Exposure on taste identification performance, measured as number of correctly identified sweet, salt, sour, and bitter taste stimuli at low, medium and high concentrations, was studied annually from 1976 to 2003 for the sensory panel at Matforsk AS. This longitudinal study of taste identification performance of 21 sensory panellists showed that after correction for the general performance level for each participant, panellist age progress (“Ageing”), number of years of panellist employment (“Experience”) and number of identification tests taken (“Exposure”) were all positively related to correct taste identification. PLS regression was employed in order to balance between estimation precision and interpretation specificity in light of the partial confounding between the explanatory variables Ageing, Experience and Exposure. The latter variable appeared to be the primary predictor of over-all taste identification performance as well as for taste identification of individual stimuli. The most prevalent mis-identifications (apart from misses involving water) were the low sucrose concentration reported as bitter taste, the low citric acid concentration reported as bitter taste, and the low caffeine/quinine concentration reported as sour.

Effects of sweet and bitter gustatory stimuli in anorexia nervosa on EEG frequency spectra

The possible differences in processing gustatory stimuli in anorexic patients compared to healthy control subjects was investigated by electrophysiological methods. The electroencephalogram (EEG) was recorded in outpatients treated with anorexia nervosa (AN) and age-matched controls after exposure to sweet (milk chocolate) and bitter (black tea) taste stimuli. Power spectrum analysis was performed on EEG epochs recorded in the above conditions. Compared to controls a significantly higher percent of theta, and lower percent of alpha1 band power was found in anorexic patients, irrespective of the kind of taste effects and hemispheric side. The pattern of activation caused by sweet and bitter stimuli was found to be different in these two groups, possibly indicating altered gustatory processing mechanisms in AN.

Taste confusions following gymnemic acid rinse.

The effect of a gymnemic acid (GA) rinse, which simulated a sweet-taste deficit, was measured on human taste perception and identification. Taste ratings showed that GA reduced the intensities of sucrose and aspartame to 14% of pre-rinse levels; over the recovery interval of 30 min, these values increased linearly to 63% of the pre-rinse levels. Repeated presentations of a set of 10 stimuli (five primarily or partly sweet--sucrose, aspartame, and NaCl-sucrose, acid-sucrose and quinine-sucrose mixtures; and five nonsweet--NaCl, KCl, Na glutamate (MSG), quinine HCl and citric acid) for identification following water and GA rinses produced 'taste confusion matrices' (TCMs). Correct identification of the sweet-tasting stimuli was reduced by 23% in presentations closely following the GA rinse, an effect that dissipated with time. Most misidentifications involved sucrose and mixtures containing sucrose. In a second TCM experiment, GA was presented frequently within each session to maintain the sweet taste deficit, which revealed itself as specific confusions. Rinsing with GA impaired discriminability of sweet-nonsweet pairs of stimuli but enhanced discriminability of the aspartame-(NaCl-sucrose) pair. GA had no effect on discriminability of nonsweet stimulus pairs. The results suggest that specific error patterns in the TCM could be used to identify quality-specific taste disorders.

Ethanol‐Induced Conditioned Taste Aversion in BXD Recombinant Inbred Mice

Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.

Differential Expression of α-Gustducin in Taste Bud Populations of the Rat and Hamster

The G-protein subunit alpha-gustducin, which is similar to rod transducin, has been implicated in the transduction of both sweet- and bitter-tasting substances. In rodents, there are differences in sensitivity to sweet and bitter stimuli in different populations of taste buds. Rat fungiform taste buds are more responsive to salts than to sweet stimuli, whereas those on the palate respond predominantly to sweet substances. In contrast, hamster fungiform taste buds are more sensitive to sweet-tasting stimuli. Taste buds in the vallate and foliate papillae of both species are sensitive to bitter compounds. These differences in sensitivity should be reflected in the numbers of gustducin-containing cells in different taste bud populations. We examined taste buds in the rat and hamster for immunoreactivity to an antibody against alpha-gustducin. Immunofluorescence of labeled taste cells was examined by confocal microscopy, and the cells were counted. Gustducin-positive cells were seen in all taste bud regions; they were spindle-shaped, with circular cross-sections and apical processes that extended to the taste pore. Cells with this characteristic shape in rat vallate taste buds are Type II (light) cells. In the rat, taste buds of the fungiform papillae had fewer gustducin-positive cells (3.1/taste bud) than those of other regions, including the posterior tongue and palate (>8.9/taste bud). Hamster fungiform taste buds contained twice as many gustducin-expressing cells (6.8/taste bud) as those of the rat. These data support the hypothesis that alpha-gustducin is involved in the transduction of both sweet- and bitter-tasting stimuli by mammalian taste receptor cells.

Three-dimensional structure of gurmarin, a sweet taste-suppressing polypeptide.

The solution structure of gurmarin was studied by two-dimensional proton NMR spectroscopy at 600 MHz. Gurmarin, a 35-amino acid residue polypeptide recently discovered in an Indian-originated tree Gymnema sylvestre, selectively suppresses the neural responses of rat to sweet taste stimuli. Sequence-specific resonance assignments were obtained for all backbone protons and for most of the side-chain protons. The three-dimensional solution structure was determined by simulated-annealing calculations on the basis of 135 interproton distance constraints derived from NOEs, six distance constraints for three hydrogen bonds and 16 dihedral angle constraints derived from coupling constants. A total of 10 structures folded into a well-defined structure with a triple-stranded antiparallel beta-sheet. The average rmsd values between any two structures were 1.65 +/- 0.39 A for the backbone atoms (N, C alpha, C) and 2.95 +/- 0.27 A for all heavy atoms. The positions of the three disulfide bridges, which could not be determined chemically, were estimated to be Cys3-Cys18, Cys10-Cys23 and Cys17-Cys33 on the basis of the NMR distance constraints. This disulfide bridge pattern in gurmarin turned out to be analogous to that in omega-conotoxin and Momordica charantia trypsin inhibitor-II, and the topology of folding was the same as that in omega-conotoxin.

Central opioid receptor subtype antagonists differentially reduce intake of saccharin and maltose dextrin solutions in rats

Opioid modulation of ingestion includes general opioid antagonism of deprivation-induced water intake and intake of sucrose and saccharin solutions. Previous studies using selective subtype antagonists indicated that opioid effects upon deprivation-induced water intake occured through the mu 2 receptor and that opioid effects upon sucrose intake occured kappa and mu 2 receptors. The present study compared the effects of intracerebroventricular administration of opioid receptor subtype antagonists upon intakes of saccharin solution and a maltose dextrin (MD) solution to determine which receptor subtypes were involved in modulation of ingestion of different preferred tastants. Significant reductions in saccharin intake (1 h) occured following naltrexone (20–50 μg: 66%) and naltrindole (delta, 20 μg: 75%), whereas [ d-Ala 2, Leu 5, Cys 6]-enkephalin (DALCE, delta 1, 40 μg: 45%) had transient (5 min) effects. Neither beta-funaltrexamine (B-FNA, mu), naloxanazine (mu 1, nor nor-binaltorphamine (Nor-BNI, kappa) significantly altered saccharin intake. Significant reductions in MD intake (1 h) occured following naltrexone (5–50 μg: 69%) and B-FNA (1–20 μg: 38%). MD intake was not reduced by naltrindole, DALCE, naloxanazine and Nor-BNI. Peak antagonist effects were delayed (20–25 min) to reflect interference with the maintenance, rather than the initiation of saccharin or MD intake. Comparisons of opioid antagonist effects across intake situations revealed that naltrexone had consistently low ID 40 values for saccharin (29 nmol), MD (25 nmol), sucrose (6 nmol) and deprivation (38 nmol) intake. Despite its significant effects relative to naloxanazine, B-FNA had significantly higher ID 40 values for saccharin (800 nmol), MD (763 nmol) and sucrose (508 nmol) relative to deprivation (99 nmol) intake, suggesting that mu 2 receptors may be mediating maintenance of intake rather than taste effects. Nor-BNI had low 40 values intake of sucrose (4 nmol), but not for saccharin (168 nmol), MD (153 nmol) and deprivation (176 nmol), suggesting that kappa receptors may mediate ingestion of sweet-tasting stimuli. That delta (naltrindole: ID 40 = 60nmol), but not delta 1, (DALCE: ID 40 = 288nmol) antagonist consistently reduce saccharin intake suggests a role for the delta 2 receptor subtype in the modulation of hedonic orosensory signals.

Inhibition of hamster chorda tympani neural response by copper chloride

Copper chloride was evaluated as a specific inhibitor of neural responses to sweet taste stimuli in the goldern hamster (Mesocricetus auratus). The chorda tympani whole-nerve response to taste stimuli was recorded before and after the tongue was treated for 30 s with 0.01, 0.1 and 1 mM CuCl2. Sweet stimuli [sucrose, fructose, saccharin (calcium salt), D-phenylalanine], which primarily stimulate chorda tympani S fibers, and non-sweet stimuli (NaCl, NH4Cl) were used. At 0.01 mM, copper chloride had little effect. At 0.10 mM it partially inhibited responses to sucrose and saccharin, but had little effect on responses to D-Phe, fructose, NaCl, NH4Cl, or a mixture of sucrose plus L-Phe. L-Phe, which has the same chelating properties as D-Phe, is not an S-fiber stimulus and likely reduced sucrose inhibiton by chelating the cupricion. Analysis of concentration–response functions revealed that 0.1 mM copper chloride inhibited the neural response to low concentrations of sucrose by about 25%, but did not significantly inhibit high concentrations of surcrose, suggesting competitive inhibition. In contrast, 0.1 mM CuCl2 reduced saccharin responses by 25% throughtout the effective range, suggesting non-competitive inhibition. Occupation of a saccharide receptor site by copper may interfere with dimer but not monomer reception and distort the saccharin receptor site. At 1 mM, CuCl2 non-competitively inhibited responses to sucrose, fructose, saccharin and the non-sweet NaCl (an N-fiber stimulus), but not NH4Cl (an H-fiber stimulus). The mechanisms of copper chloride inhibition are difficult to establish because its effects are weak at concentrations where they are specific.

A novel peptide isolated from the leaves of Gymnema sylvestre—I. Characterization and its suppressive effect on the neural responses to sweet taste stimuli in the rat

1. 1. A new substance that suppressed selectively the neural responses of the rat to sweet taste stimuli was isolated from the leaves of Gymnema sylvestre. 2. 2. The substance was proved to be a peptide consisting of 35 amino acids and having a molecular weight of about 4,000. 3. 3. The inhibitory effect on the sweet responses appeared after treating the tongue surface with the peptide at a concentration of more than 1 × 10 −6 M.

Response properties of fibers in the hamster superior laryngeal nerve

The purpose of the present investigation was to record electrophysiological responses from single fibers in the hamster superior laryngeal nerve (SLN) that were responsive to chemical stimulation of the larynx. Twenty chemical solutions, commonly used in studies of mammalian gustatory physiology, were applied to taste buds on and around the epiglottis. These stimuli were dissolved in physiological saline. Responses were the number of impulses elicited over a 15-s period following stimulus onset, above or below the background activity elicited by a previous rinse with saline. Unlike fibers in the hamster chorda tympani or glossopharyngeal nerves, SLN units were not easily classifiable into response types. Excitatory stimuli were primarily acids and bitter-tasting stimuli, with the order of their effectiveness being urea ⪢ tartaric acid > HCl > KCl > citric acid > caffeine > quinine hydrochloride > acetic acid. The sweet-tasting stimuli and most salts other than KCl were primarily inhibitory, with the order of inhibitory effectiveness being CaCl 2 > sucrose > fructose > LiCl > NaNO 3 > Li 2SO 4 > NaCl. A hierarchical cluster analysis of fibers yielded no distinct clusters, yet differing sensitivities across the fibers were suggested. SLN fibers are highly responsive to sour and bitter stimuli, although they are not sensitive to fine differences in taste quality, as are fibers in other gustatory nerves.

Effects of gymnemic acid on the chorda tympani proper nerve responses to sweet, sour, salty and bitter taste stimuli in the chimpanzee.

In man gymnemic acid is able to abolish the sweet taste. Also in man, the neural correlate of that effect is a disappearance of the response to sweet stimuli in the taste nerves, as indicated by the observations of Diamant et al. (1965). Although a variety of other mammals also show neural responses to sweet-tasting compounds, the corresponding effect of gymnemic acid has not been demonstrated. This study presents chorda tympani proper nerve recordings from the chimpanzee before and after gymnemic acid. On the chimpanzee tongue, application of 2 ml gymnemic acid (3-10 mg X ml-1 for 3-4 min) completely abolished the taste responses to 0.0035 M acesulfam-K, 0.0018 M aspartame, 0.015 M D-tryptophan, 0.02% monellin, and 0.02% thaumatin, reduced by 75% the response to 0.3 M sucrose, and by 50% that of 0.76 M xylitol. No decrease was recorded in the responses to 0.001 M quinine, 0.1 M NaCl, 0.02 and 0.04 M ascorbic acid, 0.02 and 0.04 M citric acid. The response to the sweeteners recovered with time and the recovery was complete or nearly complete after one and a half hours. It was also found that after application of 2 ml miraculin, 3 mg X ml-1 for 3 min to the tongue the neural response to acids was about 1.5 times as large as before. Gymnemic acid applied before miraculin prevented this enhancement and gymnemic acid after miraculin depressed the enhancement by miraculin of the response to citric and ascorbic acid.

Taste and chewing as stimuli for the secretion of amylase from the parotid gland of the rabbit.

Reflex secretion of amylase was studied in response to feeding pellets and carrots. Section of the ipsilateral glossopharyngeal nerve but not of the lingual nerve reduced the secretion of amylase with carrots but not with pellets. The fluid secretion was unaffected by the nerve sections. Larger volumes were secreted with pellets than with carrots, indicating that the hardness of the food, via chewing, is the main stimulus for fluid secretion. Sweet, salty, sour and bitter taste stimuli did not produce any fluid secretion in concentrations normally used for gustatory stimulation in rabbits. In a background flow of parasympathetically secreted saliva sweet stimuli regularly caused a large increase in the amylase output, salty stimuli usually had a small effect and sour and bitter stimuli seemed to have only exceptionally a small effect. Citric acid in a high concentration caused fluid secretion, at the most at a rate of about 50% of maximum; this saliva had a high content of amylase. The results support the view that during feeding the sympathetic secretory nerves can be activated via both taste stimulation and chewing, while the parasympathetic activity is mainly influenced by chewing.

Brainstem correlates of gustatory similarity in the hamster

Responses of neurons in the nucleus tractus solitarius (NTS) and parabrachial pons (Pb pons) of the hamster to 10 gustatory stimuli were compared to behavioral similarities among these compounds. Animals were given a conditioned taste aversion to one of the 10 stimuli by pairing it with an induced gastrointestinal illness. Following this procedure, the degree of generalization of the learned taste aversion to each of the other compounds was measured. Behavioral similarity profiles were derived for each stimulus from the similarities in the generalization profiles of each pair of compounds. The across-neuron correlations in the firing rates evoked by these stimuli in the NTS cells corresponded quite well to these behavioral profiles, as did these neural correlations among Pb pontine cells, except for those correlations involving quinine. Sucrose-best cells in the Pb pons are too broadly responsive to account for the behavioral similarity functions for sweet-tasting stimuli, although other best-stimulus categories of cells (NaCl- and HCl-best) showed response profiles quite similar to the behavioral profiles, as did all best-stimulus classes of cells in the NTS.

Behavioral differences in young and aged mice: strain differences for activity measures, operant learning, sensory discrimination, and alcohol preference.

Young and aged mice of the A/J and C57BL/6J inbred strains were given a series of behavioral tests which measured activity of various kinds, emotionally, operant learning, sensory discrimination, and alcohol preference. In general, compared with young mice, aged mice were less active, similar in emotionally, learned the operant discrimination as well, but extinguished more slowly, had poorer discrimination for sweet and bitter taste stimuli, and preferred alcohol to a lesser degree. Strain differences were obtained for most of these tests, and age-strain interactions occurred frequently indicating that behavioral changes occur at different rates for groups which differ in genetic constitution.