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PubMed2005

Elucidation of mammalian bitter taste.

A family of approximately 30 TAS2R bitter taste receptors has been identified in mammals. Their genes evolved through adaptive diversification and are linked to chromosomal loci known to influence bitter taste in mice and humans. The agonists for various TAS2Rs have been identified and all of them were established as bitter tastants. TAS2Rs are broadly tuned to detect multiple bitter substances, explaining, in part, how mammals can recognize numerous bitter compounds with a limited set of receptors. The TAS2Rs are expressed in a subset of taste receptor cells, which are distinct from those mediating responses to other taste qualities. However, cells devoted to the detection of sweet, umami, and bitter stimuli share common signal transduction components. Transgenic expression of a human TAS2R in sweet or bitter taste receptor-expressing cells of mice induced either strong attraction or aversion to the receptor's cognate bitter tastant. Thus, dedicated taste receptor cells appear to function as broadly tuned detectors for bitter substances and are wired to elicit aversive behavior.

Amino Acid Sequence↗
PubMed2006

Up-regulation of Metabotropic glutamate receptor 3 (mGluR3) in rat fibrosis and cirrhosis model of persistent hypoxic condition.

Glutamate is the major excitatory neurotransmitter in the central nervous system, and evidence for peripheral glutamatergic fibers in mammals is still lacking. However, glutamate receptors have been identified in peripheral organs, including taste buds, myenteric plexus, and pancreatic islet cell. Protection against anoxic damage could also be explained by mechanisms mediated by postsynaptic mGluR2 or mGluR3, such as the inhibition of membrane excitability resulting from a reduction of cAMP formation by a G-protein-dependent modulation of ion channels. In addition, activation of mGluR3 present in glial cells may contribute to neuroprotection by enhancing the production of death. Thus, mGluR2/3 behaves potentially as a major defensive mechanism anoxia-tolerant species. There are a few reports for the regional pattern of hypoxic damage, which was inversely related to the expression of mGluR2/3. The aim of this study was to characterize the expression of mGluR3 in hypoxic liver in experimental model of rat liver. Proteomic analysis of protein extracts from CCl4-induced cirrhotic liver revealed the presence of the mGluR3. The presence of mGluR3 in the cirrhotic liver was confirmed by immunohistochemical analysis. There were a number of macrophages expressing mGluR3 mainly in the fibrous septa. After 2 weeks recovery, however, most of mGluR3 positive macrophages disappeared with collagen fibers. These results demonstrate that mGluR3 involved in the liver in response to persistent hypoxic status such as fibrotic/cirrhotic condition, and suggest that the expression of mGluR3 may be a key role functional metabolism and viability in the liver by interacting with the glutamate receptors in vivo.

Animals↗
PubMed1980

Ontogeny of chorda tympani nerve responses to gustatory stimuli in the rat.

Electrical activity (whole-nerve responses) of the chorda tympani nerve (CT) in rats at 2-110 days of age was recorded in response to chemical (0.5 M NaCl, 0.5 M LiCl, 0.5 M NH4Cl, 0.1 M citric acid) stimuli applied to the dorsal surface of the tongue. The CT of rats as young as two days of age was differentially responsive to the various chemical stimuli, and the responsiveness of the CT to 0.5 M NaCl and 0.5 M LiCl relative to 0.5 M NH4Cl increased between 20 and 34 days of age and again between 35 and 90 days of age. The responsiveness of the CT to 0.1 M citric acid relative to 0.5 M NH4Cl increased from 6--19 days of age, then decreased thereafter to adulthood. A concentration series of NH4Cl solutions (0.1 M, 0.25 M, 0.5 M and 1.0 M) revealed that the CT of rats 6--110 days of age displayed increased response magnitudes as the concentration of NH4Cl increased. The CT was responsive to mechanical and thermal stimulation of the tongue, and this responsiveness was essentially unchanged throughout development. These results show that the CT of rats as young as two days of age is differentially responsive to chemical stimuli applied to the tongue, and that CT responsiveness to chemical stimuli changes during development.

Aging↗
PubMed1981

Stimulation of the gerbil's gustatory receptors by artificial sweeteners.

Some electrophysiological and behavioral taste experiments have been undertaken to determine how the Mongolian gerbil responds to artificial sweeteners. In the electrophysiological experiment only fourteen of twenty-one sweeteners produced neural responses. The most potent compound was L-4'-cyano-3-(2,2,2-trifluoroacetamido)succinanilic acid. Halogenated derivatives were more potent stimuli than non-halogenated ones. D-Tryptophan was stimulatory while L-tryptophan was not. The electrophysiological responses to sucrose were not inhibited by the presence of non-stimulating sweeteners nor were the responses to D-tryptophan inhibited by L-tryptophan. All the compounds that were stimulatory electrophysiologically were used in the behavior experiment. Using conditioned taste aversion, the gerbils responded to 5 of the compounds as sweet, one as sweet-salty, two as sweet-bitter, one as sour and one as bitter. In addition, 3 compounds were drunk equally by all groups suggesting that they were tasteless or possessed some unknown taste quality. A correlation was found between the efficacy (Kd) of the sweet-tasting compounds (pure sweet or mixed sweet) and the sweetness ranking by humans.

Animals↗
PubMed1983

Mechanism of the water response in carp gustatory receptors: independent generation of the water response from the salt response.

The carp gustatory responses to various salts and those to distilled water after adaptation of the receptors to the salts were recorded from the palatine nerve under varying conditions. (a) As far as Na4Fe(CN)6 solution prepared freshly was used, any peak in the dose-response curve was not observed, while the solution stored overnight induced a large peak response at the low concentration region as Konishi reported. The magnitude of the water response after adaptation to the stored solution was practically equal to that after adaptation to the fresh solution, suggesting that the receptor site for the water response is different from that for the dilute salts. (b) The responses to salts depended largely on the species of both cations and anions of the salts. The responses were deceased with an increase in the lyotropic number of the anions and increased with an increase in the number above 11. The response to distilled water was practically independent of the species of both monovalent cations and anions of the salts used for the adaptation. The pH dependence of the response to 10 mM NaCl was largely different from that to distilled water after adaptation to 10 mM NaCl. (c) The water response was suppressed by the presence of electrolytes in stimulating solution; the data obtained with different species of salts were described by a single curve as a function of the ionic strength. (d) The mechanism to explain how distilled water leads to depolarization of the taste cell was discussed in terms of the electric double-layer potential.

Animals↗
PubMed1985

Neuroblastoma cell as a model for a taste cell: mechanism of depolarization in response to various bitter substances.

The mouse neuroblastoma cell (N-18 clone) was used as a model for a taste cell. The N-18 cell was found to be reversibly depolarized by various bitter substances. The minimum concentrations of bitter substances which induced depolarization (threshold concentration) varied greatly with the type of the substance. There was a good correlation between the threshold concentrations for various bitter substances in the N-18 cell and those in the human taste responses. The input membrane resistance was little changed during the depolarization induced by the bitter substances. Replacement of Na+ and Cl- with impermeable ions had practically no effect on the depolarization response to the bitter substances and reduction of calcium concentration from 1.8 to 0.2 mM led to a slight increase in the responses. It was suggested that the depolarization of the N-18 cell by bitter substances mainly stems from changes in the phase-boundary potential at the outer surface of the cell.

Animals↗
PubMed1986

Synergistic effects of 5'-nucleotides on rat taste responses to various amino acids.

Synergism between 5'-nucleotides and L-amino acids in the rat taste nerve responses was investigated. The synergism was examined between low concentration of the nucleotides which induce only a negligibly small response and various concentrations of amino acids. A marked synergism was found between 5'-nucleotides and all the amino acids examined. Purine 5'-nucleotides such as GMP, deoxy GMP, GDP, GTP, AMP or IMP exhibited the synergistic effect on the responses to amino acids, while pyrimidine 5'-nucleotides such as CMP or UMP exhibited practically no synergistic effect. The presence of GMP led to a shift of the concentration-response curves for amino acids to a lower concentration region without affecting the response of the saturation level. These curves were analyzed under the assumption that there exist two types of receptor sites with different dissociation constants for each amino acid. The results suggest that GMP leads to a decrease in dissociation constants, especially for high affinity sites without affecting maximal responses. Monosodium glutamate (Glu) itself, which is known as a typical 'flavor potentiator', exhibited no enhancing effect on the responses to 4 primary taste stimuli. The mechanism of how Glu and the 5'-nucleotides 'potentiate' flavor of food is discussed.

Amino Acids↗
PubMed1983

Palatal receptor contribution to and effects of palatal alteration on taste acuity thresholds.

To determine the contribution of the soft palate to the overall taste mechanism and the effects of palatal compromise (surgery, cleft palate, and trauma), four taste solutions representing sweet, salty, sour, and bitter were applied to the apex and base of the tongue and to the soft palate of 12 subjects in each of the control and palatally compromised groups. Each group was tested on two different occasions with the sessions 2 weeks apart and one in the morning and the other in the afternoon. Results indicate that the soft palate contributes to bitter and salty sensations to a greater degree than the other two sensations. Of these two, bitter is the more acutely experienced. Patients with compromised palates revealed higher taste acuity thresholds than the normal control group, particularly with bitter solutions. Taste acuity thresholds increased with age.

Adolescent↗
PubMed1984

Effects of oral chemical irritation on taste.

Oral irritation was induced by rinses with capsicum oleoresin and with piperine, constituents of red and black pepper, respectively. The perceived intensities of two concentrations of each of four tastants representing the four classical taste qualities were evaluated after rinsing with these irritants. Comparing taste intensity after rinses with capsicum and after control rinses with emulsifying agents or water, there were significant decrements in taste intensity of citric acid and quinine, and on one concentration of sucrose, but no effect on salt. The effects of piperine were more broad, with significant decrements in perceived intensity relative to emulsion controls for all substances.

Adult↗
PubMed1985

Gustatory effectiveness of amino acids in mice: behavioral and neurophysiological studies.

Neural responses to L- and D-amino acids were recorded from the chorda tympani in the ddy mouse and their preferences were measured using the two-bottle choice technique. Most of the D- and L-amino acids elicited neural responses above 10-30 mM, but amino acids with basic side chains and their HCl derivatives produced responses at much lower concentrations. Among 19 amino acids examined, 3 D- and 7 L-amino acids were preferred, 5 L-amino acids were avoided and 4 were neutral to mice. The behavioral threshold to initiate either preference or aversion was negatively correlated with the hedonic intensity produced in mice, but not with the neural response threshold. The preference magnitude for L-amino acids at 0.1 M was negatively correlated with both MW and hydrophobicity of side chains. A high positive correlation was noted between preference magnitude in mice and hedonic intensity in humans. The role of molecular properties of amino acids in eliciting sweetness and bitterness is discussed.

Amino Acids↗
PubMed1988

The effect of cooling on the perception of carbohydrate and intensive sweeteners.

The effect of cooling on the perceived intensity of sweetness was measured for four different compounds: glucose, fructose, aspartame and saccharin. Perceived sweetness was rated in a sip and spit paradigm when the taste solution, the tongue, or both were either held at 36 degrees C or cooled to 20 degrees C. It was discovered that for glucose and fructose perceived sweetness was significantly reduced by cooling, and that cooling the tongue reduced sweetness more than did cooling the solution. The perceived sweetness of aspartame was also lessened by cooling, but in that case the temperature of the tongue and the temperature of the solution had similar effects on sweetness. In contrast to the other compounds, the sweetness of saccharin was not affected by temperature. These results (when combined with data previously reported for sucrose) raise the possibility that as a group, carbohydrate sweeteners are affected similarly by temperature, whereas thermal effects on intensive sweeteners may be less predictable. The data thereby provide indirect support for the hypothesis that the sweet taste is mediated by more than one type of gustatory receptor.

Adult↗
PubMed1989

Acid and NaCl self-adaptation with micro-drop stimulation of fungiform papillae.

A small drop of either citric acid, HCl, or NaCl, judged to be approximately equal in magnitude, was applied to two papillae for a fixed duration (15 sec). The stimulus was then reapplied to the same papillae and judged for magnitude of sensation ("self-adaptation" design). NaCl was about 50% less intense after 15 sec of prior exposure whereas citric acid showed no significant decline and HCl showed either no decline or a significant increase in magnitude. When citric acid was tested with a longer exposure time (55 sec), significant decline in citric acid magnitude occurred for all subjects. These outcomes are discussed with regard to the problem of cutaneous irritation caused by certain stimuli and the difficulty of extracting cutaneous sensations from the sensory experience of strong concentrations of acids and salts.

Adult↗
PubMed1991

Taste of glutamate salts in young and elderly subjects: role of inosine 5'-monophosphate and ions.

Taste sensitivity to five glutamate salts (sodium glutamate, potassium glutamate, ammonium glutamate, calcium diglutamate, and magnesium diglutamate) were determined in sixteen young (mean age 25.58 years) and eighteen elderly (mean age 86.89 years) subjects. The effect of inosine 5'-monophosphate (IMP) and ions on taste perception of glutamate compounds was also investigated. The detection thresholds for glutamate salts were 5.04 times higher in elderly subjects than in young subjects; the recognition thresholds were 3.84 times higher. For young subjects, 0.1 mM IMP lowered detection and recognition thresholds for all 5 salts. A stronger concentration of IMP (1 mM) had this effect in both young and elderly groups. Elderly subjects perceived suprathreshold concentrations as less intense than young subjects. Chloride and acetate salts of sodium, potassium, and calcium reduced the detection and recognition thresholds of L-glutamic acid but had no effect sodium glutamate thresholds.

Adult↗
PubMed1991

Structure/activity relationships in the L-alanine taste receptor system of the channel catfish, Ictalurus punctatus.

In order to understand the molecular determinants of amino acid taste receptor binding and activation, structure/activity studies were performed using analogs of L-alanine in a competitive ligand binding assay and a taste neurophysiological preparation. The presence of both the amine and carboxylic acid in a charged and unhindered form is a primary requisite for a ligand to both bind and activate L-alanine receptors. Although a number of carboxylic acid derivatives are moderately good stimuli, their neural activity derives from action at receptors different from L-alanine receptors. Of the molecular parameters examined, chirality and molecular volume of the side chain are the most important factors in determining the binding and stimulatory efficacy of L-amino acid taste stimuli. Electronegativity of the side chain did not correlate with receptor site binding. Heterologous ligand-induced enhancement of the binding of L-[3H]alanine by a purified taste membrane preparation is described. Neurophysiological experiments support the hypothesis that this phenomenon may be a basis of peripheral sensory interactions.

Alanine↗
PubMed1991

Transduction mechanisms for the taste of amino acids.

Amino acids are important taste stimuli for a variety of animals. One animal model, the channel catfish, I. punctatus, possesses sensitive taste receptor systems for several amino acids. Neurophysiological and biochemical receptor binding studies suggest the presence of at least three receptor pathways: one is a relatively nonspecific site(s) responsive to short-chain neutral amino acids such as L-alanine (L-ALA); another is responsive to the basic amino acid L-arginine (L-ARG); still another is a low affinity site for L-proline (L-PRO). Several possible transduction pathways are available in the taste system of this animal model for these amino acids. One of these, formation of inositol trisphosphate (IP3) and cyclic AMP (cAMP), is mediated by GTP-binding regulatory proteins, while another involves ion channels directly activated by stimuli. L-ALA is a potent stimulus to cAMP and IP3 accumulation, while L-ARG at low concentrations is without effect. On the other hand, L-ARG and L-PRO, but not L-ALA, are able to activate stimulus-specific and cation-selective channels in taste epithelial membranes reconstituted in phospholipid bilayers at the tips of patch pipettes. Preliminary studies using mouse taste tissue demonstrate that monosodium-L-glutamate (MSG) did not enhance production of IP3 or cAMP. However, in reconstitution experiments using taste epithelium of mouse, conductance changes due to MSG are observed. The specificity of this channel(s) and its uniqueness have yet to be determined.

Amino Acids↗
PubMed1991

Are umami taste receptor sites structurally related to glutamate CNS receptor sites?

Umami tasting substances, MSG (monosodium glutamate), HG (glutamic acid), LGDE (1-glutamic acid diethyl ester), DLHCA (dl-homocysteic acid), DLAAA (dl-aminoadipic acid) and 5'GMP, were tested on the hamster and the human. Ten mM MSG was routinely used in the hamster as it elicited strong chorda tympani responses. Similar response amplitudes were found for MSG, HG, LGDE, DLAAA 10 mM, DLHCA 8 mM and sucrose 100 mM. A 5 microM concentration of 5'GMP eventually was an efficient stimulus on a few preparations. Such a low concentration is very seldom efficient as a taste stimulus in rodents, indicating a higher specificity of receptor mechanisms than what is usually found for sweet taste, for example. The synergy between MSG and 5'GMP was found in the hamster CT only for concentrations lower than those of the literature, i.e., a mixture of 12 microM 5'GMP and 2.5 mM MSG showed a reinforcement of 50% in response amplitude equivalent to a 100% increase in concentration. We take this as an evidence of an umami component in the hamster CT response to glutamate; in accordance with literature data, we could not find reinforcement for higher concentrations which were in fact near saturation. Responses to MSG, HG, LGDE, DLAAA and DLHCA, among 38 other organic stimuli, were studied in 42 hamster chorda tympani. Responses to HG, LGDE and 5'GMP, among chemoreception of these compounds used as umami tasting stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

Gustatory neural responses in preweanling mice.

Taste sensitivity of preweanling mice was studied by examining responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to various taste stimuli, and was compared to that of adult mice. In mice of 7-10 days of age, comparing to that of the CT nerve, threshold of the GL nerve for monosodium l-glutamate (MSG) was low, but those for sucrose and NaCl were high. Sensitivities to HCl and quinine-HCl were similar between the CT and GL nerves, although that to quinine-HCl was larger in the GL nerve than in the CT nerve in adult mice. Enhancement of MSG responses by addition of GMP was observed in the CT nerve but not in the GL nerve in this age group. In mice of 8-16 weeks of age, threshold of the GL nerve for MSG became higher but that for NaCl became lower. Enhancement of MSG responses by addition of GMP appeared also in the GL nerve. Inhibition of NaCl responses by amiloride was observed in the CT nerve. These results suggest that, in mice, the GL nerve is important taste input for umami substances especially during the preweanling period, whereas the CT nerve is for sweet and salty substances. Properties of umami and salt receptor systems change during the postweanling period.

Animals↗