NEUROPHYSIOLOGY AND HUMAN TASTE SENSATIONS

Taste sensations are of primary importance in food flavor. Any attempt to synthesize chemically the flavor of a natural food involves mainly taste active compounds. Many distinct taste sensations can be identified as associated with food compounds. Thirteen different taste sensations are discussed herein. These different taste sensations are differentiated on the basis of stimulus chemistry and peripheral nerve conveying the taste information. Neurophysiological examination of the peripheral nerves involved in taste reveals that the sensory neurons can, in any species, be subdivided into distinct neural groups. These different neural groups respond to distinct classes of chemicals and often display different neurophysiological characteristics. Altogether in four different species, nine functional neural taste groups can be distinguished. In many cases, these neural groups can be taken as analogs for the neural groups assumed to underly human taste sensations. Distinct human taste sensations can be considered to arise from the excitation or inhibition of different neural groups. For certain human taste sensations there are no animal neural analog groups; and for certain neural groups there are no analog human sensations.     

Olfaction and Taste: Invasive Odours and Disappearing Objects

The metaphorisation of sight and hearing, the objective senses, dominate the founding ideas, or philosophemes, of Western philosophy. The senses of taste and smell are of little relevance in the formation of conceptual knowledge or in classificatory systems; they are, by virtue of their dissolving objects, incapable of giving objective knowledge in Western metaphysics. Derrida and Ulmer developed a metaphorology that exploits the chemical basis of the subjective senses of taste and smell. The anthropology of the senses takes this questioning of metaphysics into issues of how olfaction and taste function in sociality. In the routine practices of everyday life, is olfaction able to create the sense of community that it does in rituals? Or, has the repression of smell in humanity's evolution towards ‘civilisation’ muted the connective ability of multiple odour particles? In a culture and metaphysics that presumes the separability of the self from the other and the self from the object, is there a place for senses that make a nonsense of separation and objectivity through their state of meaningful dissolution? Through philosophy's metaphorisation, has taste been stripped of its sensuousness and made a sense for aesthetics and not flavours and textures? In a metaphorics premised in judgement and discernment, can taste be a sense that founds sociality? In blurring the boundaries between self and other that are necessary to form and maintain the distinction, the dissolvability of smell and taste makes another metaphorics and other socialities possible. Of all the senses, that of smell—which is attracted without objectifying—bears clearest witness to the urge to lose oneself in and become the ‘other’. As perception and the perceived—both are united—smell is more expressive than the other senses (Horkheimer and Adorno 1979:184).     

Evolution of bitter taste receptors in humans and apes

Bitter taste perception is crucial for the survival of organismsbecause it enables them to avoid the ingestion of potentiallyharmful substances. Bitter taste receptors are encoded by agene family that in humans has been shown to contain 25 putativelyfunctional genes and 8 pseudogenes and in mouse 33 putativelyfunctional genes and 3 pseudogenes. Lineage-specific expansionsof bitter taste receptors have taken place in both mouse andhuman, but very little is known about the evolution of thesereceptors in primates. We report the analysis of the almostcomplete repertoires of bitter taste receptor genes in human,great apes, and two Old World monkeys. As a group, these genesseem to be under little selective constraint compared with olfactoryreceptors and other genes in the studied species. However, incontrast to the olfactory receptor gene repertoire, where humanshave a higher proportion of pseudogenes than apes, there isno evidence that the rate of loss of bitter taste receptor genesvaries among humans and apes.     

Experience-induced changes in sugar taste discrimination

An apparent plasticity in glucose sensitivity was first noted while studying human taste variants, but the experimental design did not rule out regression to the mean. Since then, a human taste induction hypothesis that sensitivity for a taste stimulus increases with repeated exposure to it has been supported first by experience-induced changes in taste identification of monosodium glutamate and, subsequently, in sensory detection of glutaraldehyde, as well as in psychophysical and functional magnetic resonance imaging responses to novel taste stimuli. Yet, whether such plasticity occurs for the highly familiar taste of sugar remained unconfirmed. Therefore, we tested the taste induction hypothesis for sugar using a counterbalanced design, consisting of 3 pretreatment and 2 treatment conditions. The effects over time also were followed with an additional group of participants. The results showed that 1) experience with fructose significantly increases sensitivity for the taste of a sugar, glucose; 2) there are no significant differences in the sugar sensitivity between groups of randomly assigned participants before treatments; 3) a single session of 5 brief tastings of glucose has an effect on glucose sensitivity when tested 11 or 12 days later; and 4) without continued treatment, the increased sensitivity reverses within 33 or 34 days.     

L-Amino Acids Elicit Diverse Response Patterns in Taste Sensory Cells: A Role for Multiple Receptors

Umami, the fifth basic taste, is elicited by the L-amino acid, glutamate. A unique characteristic of umami taste is the response potentiation by 5’ ribonucleotide monophosphates, which are also capable of eliciting an umami taste. Initial reports using human embryonic kidney (HEK) cells suggested that there is one broadly tuned receptor heterodimer, T1r1+T1r3, which detects L-glutamate and all other L-amino acids. However, there is growing evidence that multiple receptors detect glutamate in the oral cavity. While much is understood about glutamate transduction, the mechanisms for detecting the tastes of other L-amino acids are less well understood. We used calcium imaging of isolated taste sensory cells and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice to determine if other receptors might also be involved in detection of L-amino acids. Ratiometric imaging with Fura-2 was used to study calcium responses to monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine, with and without inosine 5’ monophosphate (IMP). The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across taste sensory cells. L-amino acids other than glutamate also elicited synergistic responses in a subset of taste sensory cells. Along with its role in synergism, IMP alone elicited a response in a large number of taste sensory cells. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex.     

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 3 mM amiloride, the responses to sweet tastants such as sugar, artificial sweetener, and sweet protein were significantly reduced. The inhibitory activity of amiloride toward 1 mM aspartame was observed in a dose-dependent manner with an IC₅₀ value of 0.87 mM. 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.     

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.     

Fingerprinting taste buds: intermediate filaments and their implication for taste bud formation

Intermediate filaments in taste organs of terrestrial (human and chick) as well as aquatic (Xenopus laevis) species were detected using immunohistochemistry and electron microscopy. During development, the potential importance of the interface between the taste bud primordium and non-gustatory adjacent tissues is evidenced by the distinct immunoreactivity of a subpopulation of taste bud cells for cytokeratins and vimentin. In human foetuses, the selective molecular marker for taste bud primordia, cytokeratin 20, is not detectable prior to the ingrowth of nerve fibres into the epithelium, which supports the hypothesis that nerve fibres are necessary for initiating taste bud development. Another intermediate filament protein, vimentin, occurs in derivatives of mesoderm, but usually not in epithelium. In humans, vimentin immunoreactivity is expressed mainly in border (marginal) epithelial cells of taste bud primordia, while in chick, vimentin expression occurs in most taste bud cells, whereas non-gustatory epithelium is vimentin immunonegative. Our chick data suggest a relationship between the degree of vimentin expression and taste bud cell proliferation especially during the perihatching period. It is suggested that surrounding epithelial cells (human) and mesenchymal cells (chick) may be contributing sources of developing taste buds. The dense perinuclear network of intermediate filaments especially in dark (i.e. non-sensory) taste disc cells of Xenopus indicates that vimentin filaments also might be associated with cells of non-gustatory function. These results indicate that the mechanisms of taste bud differentiation from source tissues may differ among vertebrates of different taxa.     

Aging Effects on Anatomy and Neurophysiology of Taste and Smell1

Taste and smell have a primary role in food ingestion. Therefore, to understand why eating habits alter in elderly people, age-related differences in the chemical senses should be investigated. In early anatomical studies, substantial decreases in numbers of taste buds in old human and mouse circumvallate papillae were observed. However, recent investigations in humans, monkeys, and rats indicate that there is not a significant loss of taste buds in old age. Neurophysiological recordings from the chorda tympani nerve, innervating taste buds in fungiform papillae, demonstrate significant but small differences in response magnitudes for some chemicals in old rats. Greater age-related differences have been observed in the olfactory sense. Numbers of receptor neurons in the rat olfactory epithelium initially increase in adults and then decline in old animals; this decline is reflected in subsequent changes in the olfactory bulb. However, numbers of synapses in the bulb per receptor neuron are increased in the oldest rats, suggesting some compensatory mechanism. Differences in degree of aging effects in taste and smell might relate to the nature of receptors: a modified epithelial cell in taste versus a neuron in smell. However, in both sensory systems, large numbers of receptors remain even in old age. Since taste bud cells and olfactory receptors turn over and are replaced throughout life, the peripheral taste and smell systems might be relatively resistant to aging effects.     

Identification and characterization of human taste receptor genes belonging to the TAS2R family

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R/T2R family of taste receptor genes. TAS2R receptors are expressed at the surface of taste receptor cells and are coupled to G proteins and second messenger pathways. We have identified, cloned and characterized 11 new bitter taste receptor genes and four new pseudogenes that belong to the human TAS2R family. Their encoded proteins have between 298 and 333 amino acids and share between 23 and 86% identity with other human TAS2R proteins. Screening of a mono-chromosomal somatic cell hybrid panel to assign the identified bitter taste receptor genes to human chromosomes demonstrated that they are located in chromosomes 7 and 12. Including the 15 sequences identified, the human TAS2R family is composed of 28 full-length genes and 16 pseudogenes. Phylogenetic analyses suggest a classification of the TAS2R genes in five groups that may reflect a specialization in the detection of specific types of bitter chemicals.     

New perspectives on taste and primate evolution: the dichotomy in gustatory coding for perception of beneficent versus noxious substances as supported by correlations among human thresholds

In various environments where primates are presently observed, as well as in forests and savannas which have been inhabited by australopithecines and early hominids, there are (or there have been presumably) categories of substances eliciting taste signals associated with stereotyped responses. Such is the case for various soluble sugars of fruits and nectars, attracting consumers, and for several plant compounds in which bitter or strongly astringent properties have a repulsive effect. The occurrence of such classes of tasty substances among natural products appears to be related to the evolutionary trends that shaped primate sensory perception (for detecting either beneficent or potentially noxious substances) in the context of a long history of coevolution between animals and plants. Here, we present original psychophysical data on humans (412 individuals aged 17-59 years) as an analogy with which to test recent evidence from electrophysiology in nonhuman primates (Hellekant et al. [1997] J. Neurophysiol. 77:978-993; Danilova et al. [1998] Ann. N.Y. Acad. Sci. 855:160-164) that taste fibers can be grouped into clusters of "best-responding fibers" with two more specific clusters, one for sugars and one for quinine and tannins. The collinearity found between human taste responses (recognition thresholds) for fructose and sucrose, as well as for quinine and tannins, is presented and discussed as another evidence of the two-direction evolutionary trend determining taste sensitivity. Salt perception appears to be totally independent of these trends. Accordingly, the appreciation of a salty taste seems to be a recent culturally learned response, and not a primary taste perception. The very existence of primary tastes is discussed in the context of evolutionary trends, past and present.     

Combined rather than separate pathways for hedonic and sensory aspects of taste in fly larvae?

In mammals, the hedonic aspects (good versus bad) and sensory aspects (i.e., the molecular quality) of taste are associated with different brain regions. Anatomical data argue against such a separation in the primary taste center of Drosophila larvae. Is only one aspect of taste represented or do both co-exist at the same location? I present evidence for a hedonic representation in the larval taste center and review anatomical and behavioral data which support the co-existence of a sensory representation of taste with a hedonic representation.     

Fataluku medicinal ethnobotany and the East Timorese military resistance

In recent years, diverse scholars have addressed the issue of the chemosensory perceptions associated with traditional medicines, nevertheless there is still a distinct lack of studies grounded in the social sciences and conducted from a cross-cultural, comparative perspective. In this urban ethnobotanical field study, 254 informants belonging to the Gujarati, Kashmiri and English ethnic groups and living in Western Yorkshire in Northern England were interviewed about the relationship between taste and medicinal perceptions of five herbal drugs, which were selected during a preliminary study. The herbal drugs included cinnamon (the dried bark of Cinnamomum verum, Lauraceae), mint (the leaves of Mentha spp., Lamiaceae), garlic (the bulbs of Allium sativum, Alliaceae), ginger (the rhizome of Zingiber officinale, Zingiberaceae), and cloves (the dried flower buds of Syzygium aromaticum, Myrtaceae). The main cross-cultural differences in taste perceptions regarded the perception the perception of the spicy taste of ginger, garlic, and cinnamon, of the bitter taste of ginger, the sweet taste of mint, and of the sour taste of garlic. The part of the study of how the five selected herbal drugs are perceived medicinally showed that TK (Traditional Knowledge) is widespread among Kashmiris, but not so prevalent among the Gujarati and especially the English samples. Among Kashmiris, ginger was frequently considered to be helpful for healing infections and muscular-skeletal and digestive disorders, mint was chosen for healing digestive and respiratory troubles, garlic for blood system disorders, and cinnamon was perceived to be efficacious for infectious diseases. Among the Gujarati and Kashmiri groups there was evidence of a strong link between the bitter and spicy tastes of ginger, garlic, cloves, and cinnamon and their perceived medicinal properties, whereas there was a far less obvious link between the sweet taste of mint and cinnamon and their perceived medicinal properties, although the link did exist among some members of the Gujarati group. Data presented in this study show how that links between taste perceptions and medicinal uses of herbal drugs may be understood as bio-cultural phenomena rooted in human physiology, but also constructed through individual experiences and culture, and that these links can therefore be quite different across diverse cultures.     

A Comparison of Collection Techniques for Gene Expression Analysis of Human Oral Taste Tissue

Variability in human taste perception is associated with both genetic and environmental factors. The influence of taste receptor expression on this variability is unknown, in part, due to the difficulty in obtaining human oral tissue that enables quantitative expression measures of taste genes. In a comparison of six current techniques (Oragene RNeasy Kit, Isohelix swab, Livibrush cytobrush, tongue saliva, cheek saliva collection, and fungiform papillae biopsy), we identify the fungiform papillae biopsy is the optimal sampling technique to analyse human taste gene expression. The fungiform papillae biopsy resulted in the highest RNA integrity, enabling amplification of all the assessed taste receptor genes (TAS1R1, TAS1R2, TAS1R3, SCNN1A and CD36) and taste tissue marker genes (NCAM1, GNAT3 and PLCβ2). Furthermore, quantitative expression was observed in a subset of taste genes assessed from the saliva collection techniques (cheek saliva, tongue saliva and Oragene RNA kit). These saliva collection techniques may be useful as a non-invasive alternative sampling technique to the fungiform papillae biopsy. Identification of the fungiform papillae biopsy as the optimal collection method will facilitate further research into understanding the effect of gene expression on variability in human taste perception.     

Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin

Variation in human taste is a well-known phenomenon. However, little is known about the molecular basis for it. Bitter taste in humans is believed to be mediated by a family of 25 G protein-coupled receptors (hT2Rs, or TAS2Rs). Despite recent progress in the functional expression of hT2Rs in vitro, up until now, hT2R38, a receptor for phenylthiocarbamide (PTC), was the only gene directly linked to variations in human bitter taste. Here we report that polymorphism in two hT2R genes results in different receptor activities and different taste sensitivities to three bitter molecules. The hT2R43 gene allele, which encodes a protein with tryptophan in position 35, makes people very sensitive to the bitterness of the natural plant compounds aloin and aristolochic acid. People who do not possess this allele do not taste these compounds at low concentrations. The same hT2R43 gene allele makes people more sensitive to the bitterness of an artificial sweetener, saccharin. In addition, a closely related gene's (hT2R44's) allele also makes people more sensitive to the bitterness of saccharin. We also demonstrated that some people do not possess certain hT2R genes, contributing to taste variation between individuals. Our findings thus reveal new examples of variations in human taste and provide a molecular basis for them.     

Sweet and bitter taste: Structure and conformations of two aspartame dipeptide analogues

The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L -aspartyl-D -α-methylphenylalanine methyl ester [L -Asp-D -(αMe)Phe-OMe] and L -aspartyl-D -alanyl-2,2,5,5-tetramethylcyclopentanyl ester [L -Asp-D -Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups formaing a zwitterionic ring with a conformation defined by ψ,χX1 = 157.7°, ?61.5° for L -Asp-D -Ala-OTMCP and 151.0°, ?68.8° for L -Asp-D -(αMe)Phe-OMe. In the second residue, a left-handed helical conformations is observed for the (αMe)Phe residue of L -Asp-D -(αMe)Phe-OMe with ?₂ = 49.0° and ψ₂ = 47.9°, while the Ala residue of L -Asp-D -Ala-OTMCP adopts a semi-exextended conformation characterized by dihedral angles ?₂ = 62.8° and ψ₂ = ?139.9°. The solid-state structure of the bitter L -Asp-D -(αMe)Phe-OMe is extended; while the crystal structure of the sweet L -Asp-D -OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L -Asp-D -(αMe)Phe-OMe are compared with those of its diastereoisomer L -Asp-L -(αMe)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.     

RETRACTED: SENSORY SUGGESTIVENESS AND LABELING: DO SOY LABELS BIAS TASTE?1

Can labels suggestively influence sensory perceptions and taste? Using a “ Phantom Ingredient” taste test, we show that the presence or absence of a labeled ingredient (soy) and the presence or absence of a health claim negatively bias taste perceptions toward a food erroneously thought to contain soy. We found a label highlighting soy content made health claims believable but negatively influenced perceptions of taste for certain segments of consumers. Our results and discussion provide better direction for researchers who work with ingredient labeling as well as for those who work with soybean products.     

Immunohistochemical detection of TAS2R38 protein in human taste cells

The sense of taste plays an important role in the evaluation of the nutrient composition of consumed food. Bitter taste in particular is believed to serve a warning function against the ingestion of poisonous substances. In the past years enormous progress was made in the characterization of bitter taste receptors, including their gene expression patterns, pharmacological features and presumed physiological roles in gustatory as well as in non-gustatory tissues. However, due to a lack in TAS2R-specifc antibodies the localization of receptor proteins within gustatory tissues has never been analyzed. In the present study we have screened a panel of commercially available antisera raised against human bitter taste receptors by immunocytochemical experiments. One of these antisera was found to be highly specific for the human bitter taste receptor TAS2R38. We further demonstrate that this antibody is able to detect heterologously expressed TAS2R38 protein on Western blots. The antiserum is, however, not able to interfere significantly with TAS2R38 function in cell based calcium imaging analyses. Most importantly, we were able to demonstrate the presence of TAS2R38 protein in human gustatory papillae. Using double immunofluorescence we show that TAS2R38-positive cells form a subpopulation of PLCbeta2 expressing cells. On a subcellular level the localization of this bitter taste receptor is neither restricted to the cell surface nor particularly enriched at the level of the microvilli protruding into the pore region of the taste buds, but rather evenly distributed over the entire cell body.