Genetics of human taste perception.

Genetic approaches are rapidly yielding new information about our sense of taste. This information comes from both molecular studies of genes encoding taste receptors and other taste-signaling components, and from studies of inherited variation in taste abilities. Our understanding of bitter taste has advanced by combined information from discovery and study of the TAS2R family of taste receptor genes, hand in hand with genetic linkage and positional cloning studies, notably on the ability to taste phenylthiocarbamide (PTC). Sweet and umami tastes, mediated by TAS1R receptors, are becoming well-characterized at the molecular genetic level, and these taste classes are now targets for linkage, positional cloning, and genetic association strategies. Salty and sour tastes are still poorly characterized in genetic terms, and represent opportunities for the future.

Relationship of papillae number to bitter intensity of quinine and PROP within and between individuals.

Subjects were asked to assess the bitterness of one 6-n-propyl-2-thiouracil (PROP) and two quinine HCl (QHCl) concentrations presented via filter papers of varying sizes. The number of taste papillae stimulated by these filter papers was counted in each individual. Whole mouth sensitivity to PROP was determined in a separate session. In support of other demonstrations of spatial summation, these data indicated that perceived bitterness intensity increased as a function of area of stimulation within subjects. Between subjects, there was a significant trend for the perceived bitterness of PROP to increase with the lingual density of fungiform papillae, although this trend was highly variable and was only demonstrable among those who showed at least moderate sensitivity to PROP. On the other hand, the number of stimulated fungiform papillae failed to account for individual differences in perceived bitterness of QHCl.

Are human taste thresholds similar on the right and left sides of the tongue?

The human tongue is a relatively symmetrical anatomical structure and is generally assumed functionally equivalent on both sides. Experimental evaluation of this assumption is complicated by the fact that psychophysical measurements tend to vary considerably across testing sessions. To address functional laterality, we determined the detection thresholds of six right-handed and six left-handed subjects for Na saccharin, NaCl, citric acid and quinine HCl. Five pairs of interwoven, left and right unilateral thresholds were obtained for each taste stimulus in 12 subjects (n = 480 separate thresholds). In most cases mean sensitivity based on multiple measurements was found to be laterally symmetrical, however, we observed a few cases of lateral asymmetry of both general and compound-specific sensitivity. Threshold values were found to vary considerably across sessions, consistent with the test-retest variability previously reported for whole mouth thresholds. We conclude that taste threshold sensitivity is equivalent on the left and right anterior tongue for most individuals. Given the occasional exceptions to this rule, however, it is advisable to employ a counterbalanced design for any experimental or clinical testing protocol in which treatments are applied asymmetrically to the tongue.

Covariation in individuals' sensitivities to bitter compounds: evidence supporting multiple receptor/transduction mechanisms.

People vary widely in their sensitivities to bitter compounds, but the intercorrelation of these sensitivities is unknown. Our goal was to investigate correlations as a function of individual sensitivities to several bitter compounds representative of different chemical classes and, from these correlations, infer the number and variety of potential bitterness transduction systems for these compounds. Twenty-six subjects rated and ranked quinine HCl, caffeine, (-)-epicatechin, tetralone, L-phenylalanine, L-tryptophan, magnesium sulfate, urea, sucrose octaacetate (SOA), denatonium benzoate, and n-propylthiouracil (PROP) for bitterness. By examining individual differences, ratings and rankings could be grouped into two general clusters--urea/phenylalanine/tryptophan/epicatechin, and quinine/caffeine/SOA/denatonium benzoate/tetralone/magnesium sulfate-none of which contained PROP. When subjects were grouped into the extremes of sensitivity to PROP, a significant difference was found in the bitterness ratings, but not in the rankings. Therefore, there are also subjects who possess diminished absolute sensitivity to bitter stimuli but do not differ from other subjects in their relative sensitivities to these compounds.

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.

Ibuprofen as a chemesthetic stimulus: evidence of a novel mechanism of throat irritation.

This paper reports a study of the oral and pharyngeal chemesthetic effects of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen [2-(4-isobutylphenyl)propanoic acid], which pilot experiments had indicated produces an unusual sensory irritation of the throat. In experiment 1 subjects swallowed aqueous solutions of ibuprofen prepared with different buffering agents and gave ratings of irritation and taste in the mouth and throat. The results showed that ibuprofen irritates the throat much more than the mouth, and that its quality in the throat is characterized primarily as sting/prick, itch and tickle (often leading to cough). Based upon the results obtained with the different buffering agents, we hypothesized that the sting/prick/itch qualities of throat irritation were pH-dependent. Parametric manipulation of solution pH in experiment 2 confirmed this hypothesis. The same experiment revealed that, in contrast to other oral irritants (e.g. capsaicin and menthol), repeated stimulation caused neither sensitization nor desensitization of throat irritation. In the final experiment we found that ibuprofen's throat irritation could not be modulated by temperature, as it should be if stimulation occurred via capsaicin-sensitive receptors. We therefore conclude that ibuprofen has novel chemesthetic properties, which are not mediated by capsaicin-sensitive (vanilloid) receptors, and that a major component of the throat irritation it produces occurs via a pH-dependent receptor mechanism.

Psychophysics of taste lateralization on anterior tongue.

There have been very few investigations of the spatial properties of taste stimuli localized to specific areas of the oral cavity. This is surprising, since the spatial localization of taste sensations may contribute to the overall taste percept, much as do quality, intensity, and the temporal characteristics of tastes. The difficulty in eliminating the confounding factor of a tactile sensation may partially account for the paucity of such studies, since a gustatory stimulus cannot be presented as a liquid without a tactile component. As a step toward understanding the localizability of gustatory sensations, we designed a yoked stimulator and an experimental procedure to control for tactile cues. Lateral discrimination was evaluated at the tip of the tongue with four taste stimuli (sodium saccharin, sodium chloride, citric acid, and quinine hydrochloride) by presenting a taste and a blank solution simultaneously at two locations on the tongue. We found that subjects could lateralize all four taste stimuli in the absence of any discriminative tactile cues. Subjects' ability to lateralize varied as a psychometric function of the stimulus concentration. Detection thresholds, measured in a forced-choice two-interval staircase procedure with the same yoked stimulator that was used in the lateralization task, were always lower than lateralization thresholds, and both lateralization and detection thresholds were correlated within subjects. Subjects were unable to lateralize taste cues on a nongustatory surface under the upper lip at the highest tested concentrations, at which performance was 100% on a gustatory surface (dorsal anterior tongue). These results show that (1) taste compounds can be lateralized in the absence of any discriminative mechanical cue (but only on the gustatory epithelium) and (2) although the localization of a compound does not logically require conscious detection of the taste (cf. blind sight), subjects always detected a taste when they were able to lateralize.

A behavioral analysis of the ingestion of glucose, maltose and maltooligosaccharide by rats.

Glucose, maltose, and Polycose are stimuli that differ in their effectiveness in stimulating ingestion in the rat. To understand better how variation in glucose chain length affects the ingestion of these compounds, we compared the effect of six concentrations of glucose, maltose, and maltooligosaccharide (MOS) on the microstructure of the licking behavior of the rat. At the three lowest concentrations the order of effectiveness in stimulating ingestion was MOS > maltose > glucose. At the three highest concentrations, there were no differences among the three compounds in volume ingested. As measured by initial rate of licking, the orosensory stimulating effectiveness of the three compounds were ordered as MOS > maltose > glucose. The magnitude of the negative feedback signals were very similar for MOS and maltose and greater than glucose at all but the highest two concentrations of glucose, suggesting that glucose chain length, not caloric density, is responsible for the differences in the magnitude of negative feedback. With the three lowest concentrations, the ordering of the compounds in their ability to stimulate intake depended on orosensory stimulating ability.

Selective removal of a target stimulus localized by taste in humans.

Recent studies have shown that people can localize a punctate gustatory stimulus on the lingual epithelium in the absence of discriminative tactile cues. The present studies examined the human ability to localize taste sensations on the tongue and to use this information to remove selectively a target stimulus (a flavored, 1 cm(3) gelatin cube) from the mouth when presented with non-target distractors that vary in number and taste. Findings indicate that humans are capable of localizing and removing either an aversive or an appetitive gustatory target from a field of tactile distractors via taste sensations alone, although this ability diminishes as the number of distractors increases (implicating serial searches, rather than parallel). In addition, humans can localize and selectively remove a target taste in the presence of distractors of another distinct taste quality. Under these conditions performance is either unaffected or reduced, which indicates that contrast with the distinct taste of the distractors does not enhance performance. Humans also are capable of removing a nearly tasteless cube from a field of flavored distractors, but this is clearly a more difficult task, suggesting that 'tactile capture' of taste occurs for the tasteless target cube and interferes with the localization of taste. Finally, perceived suprathreshold stimulus intensity did not seem to be related to the ability to localize and remove a target stimulus via taste sensations and failed to account for variations in performance across individuals.

Saccharin increases the effectiveness of glucose in stimulating ingestion in rats but has little effect on negative feedback.

To determine if oropharyngeal stimulation contributes to the magnitude of the negative feedback signal during ingestion, we tested rats on a series of solutions that varied in taste intensity but not in nutritive or osmotic properties. To do this, Na saccharin was added to a standard 0.2 M glucose solution in concentrations of 0, 0.25, 0.5, 1, 2, 4, and 8 mM. Nondeprived rats were given free access to these solutions in ascending order of concentration in 30-min tests in test cages with a lickometer that recorded the time of each lick to the nearest msec. The cumulative licking curve for each rat on each test, obtained by cumulating the number of licks in each successive minute during the test, was fit by the least squares method to an exponential function. This provides an estimate of the initial rate of licking and of the rate of decline in the rate of licking. The results were that the volume ingested increased from 6 to 26 ml and the initial rate of licking increased from 50 to 230 licks/min/min over the saccharin concentration range, but the estimates of the rate of decline of the rate of licking remained constant at about 0.06 licks/min over this range. Thus, we found no evidence for an oropharyngeal contribution to the decline in the rate of licking. Changes in the volume ingested depended solely on the initial avidity with which the rats ingested the solution.

Monogeusia for fructose, glucose, sucrose, and maltose.

We investigated the ability of subjects to discriminate sugars with a whole-mouth forced-choice paradigm, in which a standard solution was compared with a test solution of varied concentration. Discrimination probabilities were U-shaped functions of test concentration: for 6 subjects and pairwise combinations of fructose, glucose, and sucrose, discriminability always declined to chance over a narrow range of test concentrations. At concentrations < or = 100 mM, maltose was indiscriminable from fructose but discriminable at higher concentrations for 4 subjects. By analogy with the monochromacy of night vision, whereby any two lights are indiscriminable when their relative intensities are suitably adjusted, we call the gustatory indiscriminability of these sugars monogeusia. The simplest account of monogeusia is that all information about the indiscriminable sugars is represented by a single neural signal that varies only in magnitude. The discriminability of maltose from the other sugars at higher concentrations is consistent with the hypothesis that maltose also activates a second gustatory code.

Suppression of bitterness by sodium: variation among bitter taste stimuli.

Taste interactions between salts (NaCl, LiCl, KCl, L-arginine:L-aspartic acid, Na-acetate and Na-gluconate) and bitter-tasting compounds (urea, quinine HCl, magnesium sulphate, KCl, amiloride HCl and caffeine) were investigated. In each study binary combinations of three or four concentrations of one bitter compound with four concentrations (0, 0.1, 0.3 and 0.5 M) of one salt were rated for bitterness and saltiness using the method of magnitude estimation. In most cases, perceived bitterness was suppressed by salts, although the degree of suppression varied. In general, bitterness suppression was not accompanied by an equivalent reciprocal suppression of saltiness. Only MgSO4 and amiloride had suppressing effects on the saltiness of NaCl at the intermediate concentrations and no bitter compound affected the saltiness at the high concentrations of NaCl. Since salt suppressed the bitterness of urea effectively, a detailed analysis of suppression of the bitterness of urea by different salts was conducted. Those studies indicated that the key component in this effect was the sodium or lithium ion for two reasons: first, all three sodium salts and the lithium salt had a suppressive effect on bitterness, whereas KCl did not; secondly, the effect of a salt on suppression of the bitterness of urea was independent of its perceived saltiness; that is, NaCl, Na-acetate (which is perceived as less salty than NaCl), and Na-gluconate (which is perceived as less salty than Na-acetate) reduced bitterness comparably. These results suggest that there is a major peripheral component to the suppression of the bitterness of urea, and perhaps other bitter tasting compounds, by sodium.

Sodium specificity of salt appetite in Fischer-344 and Wistar rats is impaired by chorda tympani nerve transection.

Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference for NaCl and displays more aversive and fewer ingestive oral motor responses to orally infused NaCl when tested in sodium balance. Despite these differences, F344 rats show an increase in preference for NaCl in response to sodium depletion. The present study was designed to determine whether the salt appetite of sodium-depleted F344 rats is cation specific and whether such selectivity is mediated in part by an intact chorda tympani nerve. Sodium-depleted (10 mg furosemide) F344 (n = 13) and Wistar (n = 16) rats were permitted repeated access to nine stimuli (water, and 0.05 and 0.3 M NaCl, KCl, NH4Cl, and CaCl2), presented randomly in 10-s trials. One-half of the rats had their chorda tympani nerve sectioned (CTX). Under conditions of sodium depletion, both strains discriminated NaCl from other chloride salts. CTX significantly impaired the selectivity of the licking behavior in both strains, suggesting that sodium-specific licking is partially mediated by anterior tongue taste receptors. These findings suggest that both sodium-depleted F344 and Wistar rats are comparable in their abilities to recognize NaCl, to distinguish it from other salts, and to respond selectively to it, despite the fact that sodium-replete F344 and Wistar rats differ greatly in their NaCl preference.

Lick rate analysis of sodium taste-state combinations.

The combined effects of taste and physiological state on lick rate for NaCl were systematically evaluated in two experiments. In experiment 1 the lick rates of six groups of rats (Sprague-Dawley) were recorded during the first 3 min of a NaCl drinking bout, where each group received a different concentration. Half of the rats were depleted by injections of the diuretic-natriuretic furosemide (10 mg ip), whereas the other half were not. The inverted U-shaped concentration-response functions for sodium-replete rats peaked approximately at isotonicity. The replete lick rate function was uniformly elevated for rats examined in the sodium-depleted state. In experiment 2 each rat received access to all six solutions within a 40-min test session. Rats were tested twice, once in positive and once in negative sodium balance. The solutions were repeatedly presented in counterbalanced order in a series of 10-s exposures. The replete and deplete functions of the within-group study closely resembled those of the between-group study. When the deplete rats' function was divided into three segments coinciding with the beginning, middle, and end of the 40-min session, the functions were shifted down vertically but retained their shape. In general, sodium-state level dramatically affected the absolute lick rates but did not appear to shift the location of the concentration-response function along the horizontal (i.e., concentration) axis. The form of the function appears to have been determined by oral factors alone.

Chorda tympani section decreases the cation specificity of depletion-induced sodium appetite in rats.

Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectively to NaCl after chorda tympani nerve (CTn) section (CTX). A variety of chloride salts (NaCl, KCl, NH4Cl, CaCl2) at two concentrations (0.05 and 0.3 M) were presented semirandomly to sodium-deplete rats in repeated single-stimulus trials (10 s). The responses of sodium-depleted surgical control rats (n = 8) were highly cation specific. These rats licked substantially more for both sodium stimuli than for any other chloride salt. On the other hand, the licking responses of CTX sodium-depleted rats (n = 8) were less cation selective. These rats licked NaCl and 0.05 M KCl at comparable rates. For both NaCl concentrations, CTX rats had significantly lower lick rates than controls. In addition, the difference between the lick rate for NaCl and that for the other salts was much greater for control rats than for CTX rats. Although CTn section did not entirely eliminate the high levels of responsivity to NaCl observed in the intact sodium-depleted rat, it did substantially compromise the selectivity of the behavior, which suggests that the input of the CTn is critical for taste-guided sodium specific behaviors.

A quantitative comparison of taste reactivity behaviors to sucrose before and after lithium chloride pairings: a unidimensional account of palatability.

Alterations in the motivation to ingest sucrose can be quantified by measuring the number and type of oral motor and somatic responses (i.e., taste reactivity [TR]) that are elicited by sucrose. In 2 experiments, rats had intraorally infused sucrose paired with LiCl injections for several trials, or they were injected with LiCl and had sucrose infused every 5 min during the 30-min postinjection period (data from Spector, Breslin, & Grill, 1988). In both experiments, ingestive TR responses decreased, whereas aversive TR responses increased over trials. Individual response components that comprise the ingestive and aversive categories followed the same trends of increase or decrease but changed at different rates as a function of number of trials or exposures. Overall, the array of response components could be projected onto a single unidimensional scale of palatability to capture the motivational states that ranged from acceptance to rejection.