Regional specificity of chlorhexidine effects on taste perception

Chlorhexidine (CHX) gluconate, a bitter bis-biguanide antiseptic, reduces the intensity of the salty taste of NaCl and bitter taste of quinine in humans. This study addresses regional specificity of CHX's effects on taste. Perceptual intensity and quality were measured for separate taste bud containing oral loci innervated either by afferent fibers of cranial nerve (CN) VII or CN IX. Measurements were obtained following three 1-min oral rinses with either 1.34 mM CHX or water, the control rinse. CHX rinse reduced the intensity of NaCl more at the tongue tip and palate than at posterior oral sites. Thus, fungiform and palatal salt-taste receptors may differ from salt-taste receptors of the foliate and circumvallate taste papillae. The intensity of quinine.HCl was reduced equally by CHX at all sites tested but was frequently tasteless on the less sensitive anterior sites, suggesting quinine receptor diversity. In rodents, a portion of NaCl-taste receptors in the receptive field of CN VII is sensitive to the epithelial Na+ channel blocker amiloride and a portion is amiloride insensitive; all CN IX receptors are amiloride insensitive. The current results are the first to suggest that there may also be distinct, regionally specific populations of NaCl-taste receptors in humans.     

Effect of compound sequence on bitterness enhancement

The nature and occurrence of carry-over effects, i.e. the response to a stimulus is influenced by previous samples, were examined for selected bitter compounds. A time-intensity procedure was used to rate the bitterness of six compounds (caffeine, denatonium benzoate, limonin, naringin, quinine and sucrose octa-acetate). For each subject concentrations of these compounds were determined that were approximately equal in intensity to 1.18 x 10(-5) M limonin. To test carry-over effects of each compound the 36 paired sequences (pairs) were evaluated. Within a session three pairs were tested, between which two-stage rinses were used to remove any effects of the previous pairs. Within a pair only water rinses were used between stimuli. For all compounds carry-over or sensitization effects were observed in which values for maximum intensity, rate of onset and total area under the time-intensity curve were higher for a compound when tested in the second position than in the first. In addition, the degree of sensitization and susceptibility to sensitization were compound-specific. Caffeine increased the bitterness by the largest amount for all other compounds, while it was least affected. Regardless of the compound in the first position, the bitterness of quinine and denatonium were most enhanced.     

Stimulation of bitterness by capsaicin and menthol: differences between lingual areas innervated by the glossopharyngeal and chorda tympani nerves

Capsaicin is viewed as a purely chemesthetic stimulus that selectively stimulates the somatosensory system. Here we show that when applied to small areas of the tongue, capsaicin can produce a bitter taste as well as sensory irritation. In experiment 1, individuals were screened for the ability to perceive bitterness from capsaicin on the circumvallate papillae. Fifteen of 25 subjects who reported at least weak bitterness rated the intensity of taste, irritation and coolness produced by 100-320 microM capsaicin and 100-320 mM menthol applied via cotton swabs to the tip (fungiform region), the posterior edge (foliate region), and the dorsal posterior surface (circumvallate region) of the tongue. Sucrose, citric acid, sodium chloride and quinine hydrochloride were applied to the same areas to assess tastes responsiveness. On average, capsaicin and menthol produced "moderate" bitterness (and no other significant taste qualities) in the circumvallate region, and weaker bitterness on the side and tip of the tongue. Sensory irritation from capsaicin was rated significantly higher at the tongue tip, whereas menthol coolness was rated higher in the circumvallate region. In experiment 2 we applied sucrose and quinine hydrochloride together with capsaicin to investigate the effects other taste stimuli might have on capsaicin's reported bitterness. As expected, adding quinine produced stronger bitterness in the circumvallate and fungiform regions, and adding sucrose significantly reduced the bitterness of capsaicin in the circumvallate region. Overall, the results suggest that capsaicin and menthol are capable of stimulating a subset of taste neurons that respond to bitter substances, perhaps via receptor-gated ion channels like those recently found in capsaicin- and menthol-sensitive trigeminal ganglion neurons, and that the glossopharyngeal nerve may contain more such neurons than the chorda tympani nerve. That some people fail to perceive bitterness from capsaicin further implies that the incidence of capsaicin-sensitive taste neurons varies across people as well as between gustatory nerves.     

Measures of individual differences in taste and creaminess perception

Previous reports that the sensitivity to the bitter tasting substance 6-n-propylthiouracil (PROP) is related to the sensitivity to other tastes, to chemical irritants, and to fats and oils have led to adoption of PROP as a measure of general oral sensitivity and as a predictor of dietary habits that could impact health. The results, however, have not been consistent. It was recently discovered that the ability to perceive "thermal taste" (i.e., sweetness from thermal stimulation alone) was associated with higher responsiveness to 4 prototypical taste stimuli but not to PROP. This finding implied that individual differences in taste perception are determined in large part by factors other than those related to genetic expression of the PROP receptor. The present study followed up this observation by comparing individual differences in perception of 4 prototypical taste stimuli (sucrose, NaCl, citric acid, and quinine) and PROP under conditions that also enabled assessment of the reliability of individual intensity ratings of taste. Creaminess ratings of 3 milk products that had different fat contents were also collected to investigate further the relationship between taste and oral somatosensory perception. The results showed that intensity ratings across 2 trials were significantly correlated for all 5 taste stimuli and that averaging across replicates led to significant correlations among the 4 prototypical stimuli. In contrast, the bitterness of PROP was correlated only with the bitterness of quinine. None of the taste stimuli, including PROP, was significantly correlated with ratings of creaminess. These results imply 1) that with the exception of PROP, as few as 2 intensity ratings of common taste stimuli can reveal individual differences in overall taste perception and 2) that any relationship between taste and oral sensation is too weak to be detected under the same conditions. Accordingly, the results support other evidence that the genetic factors which determine the ability to perceive PROP do not play a major role in overall taste and oral somatosensory perception.     

Tactile interaction with taste localization: influence of gustatory quality and intensity

Taste is always accompanied by tactile stimulation, but little is known about how touch interacts with taste. One exception is evidence that taste can be "referred" to nearby tactile stimulation. It was recently found (Lim J, and Green BG. 2007. The psychophysical relationship between bitter taste and burning sensation: evidence of qualitative similarity. Chem Senses. 32:31-39) that spatial discrimination of taste was poorer for bitterness than for other tastes when the perceived intensities were matched. We hypothesized that this difference may have been caused by greater referral of bitterness by touch. The present study tested this hypothesis by comparing localization of quinine sulfate and sucrose under conditions that minimized and maximized the opportunity for referral. In both conditions, stimulation was produced by 5 cotton swabs spaced 1 cm apart and arranged in an arc to enable simultaneous contact with the front edge of the tongue. Only one swab contained the taste stimulus, whereas the rest were saturated with deionized water. In both conditions, the swabs were stroked up-and-down against the tongue 5 times. Subjects were asked to identify which swab contained the taste stimulus 1) 5 s after the fifth stroke (touch-removed condition) and 2) immediately at the end of the fifth stroke, with the swabs still in contact with the tongue (touch-maintained condition). Ratings of taste intensity were obtained to assess the possible effect of perceived intensity on spatial localization. Taste localization was surprisingly accurate, especially for sucrose, with errors of localization in the range of 1 cm or less. For both stimuli, localization tended to be poorer when the tactile stimulus was present while subjects made their judgments, but the difference between conditions was significant only for the lower concentration of quinine. The results are discussed in terms of both the surprisingly good spatial acuity of taste and the possibility of having a close perceptual relationship between touch and bitter taste.     

Two-stimulus versus one-stimulus procedure in the framework of functional measurement: a comparative investigation using quinine HCl/NaCl mixtures

When subjects are requested to judge single stimuli the observableresponses are the result of both sensory and judgmental processes.De Graaf et al. (1987) employed functional measurement in combinationwith a two-stimulus procedure in order to separate these twotypes of processes. This paper discusses the results of twoexperiments investigating taste interactions in quinine HCl/NaClmixtures. The first experiment employed a one-stimulus procedure,the second experiment employed De Graaf et al.'s two-stimulusprocedure. Comparing the two procedures, the main advantageof the one-stimulus procedure seems to lie in its simplicity.In addition, it enables the determination of a scale value forwater. However, the obtained ratings are context-dependent andare affected by end effects of the response scale. The mostimportant benefit of the two-stimulus procedure is that it allowsfor a post-experimental verification of the linearity of theresponse-output function. This check ensures that all scalevalues are assessed on an interval scale. If water can be assumedto be tasteless, ratio scale values can be obtained. It wasshown that quinine bitterness is largely suppressed by NaCl,whilst the saltiness intensity elicited by NaCl remains virtuallyunaffected. In both experiments, the perceived total taste intensityof a mixture could be well predicted by the weighted sum ofthe saltiness and bitterness sensations within the mixture percept.     

Taste confusions following chlorhexidine treatment.

Chlorhexidine, a bitter bis-biguanide antiseptic, is the only known blocker of the human salty taste. In order to characterize the effects of chlorhexidine on stimulus identification, taste confusion matrix (TCM) performance was measured for subjects treated with 1.34 mM chlorhexidine gluconate (n = 9) and water controls (n = 9). Ten stimuli [water, 0.1 M NaCl, 0.1 M KCl, 0.1 mM quinine-HCl (QHCl), 0.1 M monosodium glutamate (MSG), 3 mM citric acid, 0.3 M sucrose and mixtures of NaCl, QHCl and citric acid with sucrose] were presented in 10 replicates for identification from a list of 10 stimulus names. T(10), a measure of performance consistency from information theory, was lower for chlorhexidine-treated subjects (2.02 +/- 0.11 bits) than controls (2.73 +/- 0.11 bits) (P < 0.0001). T(2), an indirect measure of pairwise stimulus discrimination, approached chance levels (0.40 bit) in chlorhexidine-treated subjects for all possible pairs of NaCl, KCl, QHCl and water, as well as pairs composed of sucrose and the NaCl-sucrose and quinine-sucrose mixtures. In controls T(2) values approached perfect scores (1.00 bit) for all stimulus pairs except NaCl-KCl and NaCl-MSG. The results demonstrate a decreased ability to identify taste stimuli that is consistent with alterations in the ability of stimuli to elicit salty and bitter taste perceptions. As a selective, effective, persistent and reversible blocker of taste perceptions, chlorhexidine should prove useful in defining taste mechanisms in humans.     

Conductance Change Associated with Receptor Potentials of Gustatory Cells in Rat

The electrical properties of gustatory cells and cells which do not respond to chemical stimuli in the taste bud of fungiform papillae in rats were studied by means of intracellular microelectrodes. Neither of these cell types showed spike electrogenesis. Gustatory cells showed a depolarization, the receptor potential, associated with an increase in the membrane conductance in response to NaCl, sucrose, and HCl, whereas quinine produced a decrease in the conductance together with an increase in the receptor potential magnitude. The reversal point of the receptor potential in response to NaCl or KCl was close to zero membrane potential, but in the case of quinine it was at a more negative potential level than the resting potential. From these results two receptive processes are postulated in the gustatory cell membrane. When the gustatory cells were stimulated for a long duration by concentrated NaCl or sucrose, receptor potentials showed adaptation with decrease in magnitude, but adaptation of the responses to HCl and quinine were hardly detected. Adaptation of the receptor potential was not correlated with conductance change.     

Response properties of macaque monkey chorda tympani fibers

Many of the chorda tympani fibers of crab-eating monkeys respond to more than one of the four basic stimuli (NaCl, sucrose, HCl, and quinine hydrochloride) as well as cooling or warming of the tongue. Fibers could be classified into four categories depending on their best sensitivity to any one of the four basic stimuli. Sucrose-best and quinine-best fibers are rather specifically sensitive to sucrose and quinine, respectively, while salt-best and acid-best fibers respond relatively well to HCl and NaCl, respectively. Saccharin, dulcin, and Pb acetate produce a good response in sucrose-best fibers, but quinine- best and salt-best fibers also respond to saccharin. Highly significant positive correlations exist between amounts of responses to sucrose and those to saccharin, dulcin, and Pb acetate, indicating that these substances produce in the monkey a taste quality similar to that produced by sucrose. Compared with chroda tympani fibers of rats, hamsters, and squirrel monkeys, macaque monkey taste fibers are more narrowly tuned to one of the four basic taste stimuli and more highly developed in sensitivity to various sweet-tasting substances. Also LiCl and NaCl are more effective stimuli for gustatory receptors in macaque monkeys than NH4Cl and KCl. This contrasts with a higher sensitivity to KCl and NH4Cl than to NaCl in chorda tympani fibers of squirrel monkeys.     

Generalization of conditioned taste aversions in hamsters: evidence for multiple bitter receptor sites

Multiple bitter receptor sites appear to exist within the hamstergustatory system supporting the data of other investigatorson humans, rats and frogs. The sodium salts of four anions,m-nitrobenzene sulfonate (NBSA), picrate, m-nitrobenzoate (NBA)and cholate, were tested in two-bottle preference tests andfor generalization to a variety of stimuli in a conditionedtaste aversion (CTA) paradigm. All four of these anions arebitter to humans. One, NBSA, generalized to sucrose suggestinga sweet taste, while the remaining three appear to be bitterwith varying degrees of saltiness. The bitterness of these threeanions to hamsters appears to be perceptually different froma quinine-type bitterness. Separate bitter receptor sites areindicated for quinine and urea, plus a third site acceptingNBA, picrate and cholate. More bitter sites are plausible. Separatesites for quinine and urea appear to occur across species. Itwas also concluded that quinine does not serve as a prototypicbitter stimulus for all bitters in the CTA test.     

Effects of isoproterenol treatment on gustatory neural responses in three inbred strains of mice

1. Treatment of a beta-agonist, isoproterenol, for 5 days reduced chorda tympani responses to sucrose by about 40% of the control without affecting responses to other taste stimuli, such as NaCl, HCl and quinine HCl, in balb CrSlc mice whereas such reduction of sucrose responses was not observed in C57BL/6-CrSlc and C3H/HeSlc mice, although in the latter two strains long-lasting off-responses to quinine HCl appeared after the treatment. 2. In BALB mice, the magnitude of reduction of sucrose responses by isoproterenol increased with prolonging the treatment from 1 to 5 days, although it reached almost its maximum level by the 3 days treatment. 3. BALB mice with the removal of the submandibular glands showed slightly greater control responses of the chorda tympani nerve to sucrose than BALB mice with the sham-operation or the removal of the sublingual glands, and showed no significant reduction of sucrose responses by isoproterenol treatment. 4. These results suggest that isoproterenol probably did not act directly on sweetener receptors of taste cell membranes but affect them through the submandibular salivary system.     

Bitter taste stimuli induce differential neural codes in mouse brain

A growing literature suggests taste stimuli commonly classified as "bitter" induce heterogeneous neural and perceptual responses. Here, the central processing of bitter stimuli was studied in mice with genetically controlled bitter taste profiles. Using these mice removed genetic heterogeneity as a factor influencing gustatory neural codes for bitter stimuli. Electrophysiological activity (spikes) was recorded from single neurons in the nucleus tractus solitarius during oral delivery of taste solutions (26 total), including concentration series of the bitter tastants quinine, denatonium benzoate, cycloheximide, and sucrose octaacetate (SOA), presented to the whole mouth for 5 s. Seventy-nine neurons were sampled; in many cases multiple cells (2 to 5) were recorded from a mouse. Results showed bitter stimuli induced variable gustatory activity. For example, although some neurons responded robustly to quinine and cycloheximide, others displayed concentration-dependent activity (p<0.05) to quinine but not cycloheximide. Differential activity to bitter stimuli was observed across multiple neurons recorded from one animal in several mice. Across all cells, quinine and denatonium induced correlated spatial responses that differed (p<0.05) from those to cycloheximide and SOA. Modeling spatiotemporal neural ensemble activity revealed responses to quinine/denatonium and cycloheximide/SOA diverged during only an early, at least 1 s wide period of the taste response. Our findings highlight how temporal features of sensory processing contribute differences among bitter taste codes and build on data suggesting heterogeneity among "bitter" stimuli, data that challenge a strict monoguesia model for the bitter quality.     

棉铃虫幼虫对人类呈味物质的取食反应

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

The influence of sodium salts on binary mixtures of bitter-tasting compounds

In order to study potential mixture interactions among bitter compounds, selected sodium salts were added to five compounds presented either alone or as binary bitter-compound mixtures. Each compound was tested at a concentration that elicited 'weak' perceived bitterness. The bitter compounds were mixed at these concentrations to form a subset of possible binary mixtures. For comparison, the concentration of each solitary compound was doubled to measure bitterness inhibition at the higher intensity level elicited by the mixtures. The following sodium salts were tested for bitterness inhibition: 100 mM sodium chloride (salty), 100 mM sodium gluconate (salty), 100 and 20 mM monosodium glutamate (umami), and 50 mM adenosine monophosphate disodium salt (umami). Sucrose (sweet) was also employed as a bitterness suppressor. The sodium salts differentially suppressed the bitterness of compounds and their binary combinations. Although most bitter compounds were suppressed, the bitterness of tetralone was not suppressed, nor was the bitterness of the binary mixtures that contained it. In general, the percent suppression of binary mixtures of compounds was predicted by the average percent suppression of its two components. Within the constraints of the present study, the bitterness of mixtures was suppressed by sodium salts and sucrose independently, with few bitter interactions. This is consistent with observations that the bitter taste system integrates the bitterness of multi-compound solutions linearly.     

Taste perception with age: generic or specific losses in supra-threshold intensities of five taste qualities?

The influence of ageing on supra-threshold intensity perception of NaCl, KCl, sucrose, aspartame, acetic acid, citric acid, caffeine, quinine HCl, monosodium glutamate (MSG) and inosine 5'-monophosphate (IMP) dissolved in water and in 'regular' product was studied in 21 young (19-33 years) and 21 elderly (60-75 years) persons. While the relative perception (intensity discrimination) seems to be remarkably resistant to the effect of ageing, the absolute perception (intensity rating) decreased with age for all tastants in water, but only for the salty and sweet tastants in product. When assessed while wearing a nose clip, only the perception of salty tastants was diminished with age. The slopes of the psychophysical functions were flatter in the elderly than in the young for the sweet, bitter and umami tastants in water, and for the sour tastants in product only. The age effects found were almost exclusively generic and never compound-specific within a taste. This study indicates that the relevance of determining intensities of tastants dissolved in water for the 'real life' perception of taste in complex food is rather limited.     

Cross-adaptation and bitterness inhibition of L-tryptophan, L-phenylalanine and urea: further support for shared peripheral physiology

A previous study investigating individuals' bitterness sensitivities found a close association among three compounds: L-tryptophan (L-trp), L-phenylalanine (L-phe) and urea (Delwiche et al., 2001, Percept. Psychophys. 63, 761-776). In the present experiment, psychophysical cross-adaptation and bitterness inhibition experiments were performed on these three compounds to determine whether the bitterness could be differentially affected by either technique. If the two experimental approaches failed to differentiate L-trp, L-phe and urea's bitterness, then we may infer they share peripheral physiological mechanisms involved in bitter taste. All compounds were intensity matched in each of 13 subjects, so the judgments of adaptation or bitterness inhibition would be based on equal initial magnitudes and, therefore, directly comparable. In the first experiment, cross-adaptation of bitterness between the amino acids was high (>80%) and reciprocal. Urea and quinine-HCl (control) did not cross-adapt with the amino acids symmetrically. In a second experiment, the sodium salts, NaCl and Na gluconate, did not differentially inhibit the bitterness of L-trp, L-phe and urea, but the control compound, MgSO(4), was differentially affected. The bitter inhibition experiment supports the hypothesis that L-trp, L-phe and urea share peripheral bitter taste mechanisms, while the adaptation experiment revealed subtle differences between urea and the amino acids indicating that urea and the amino acids activate only partially overlapping bitter taste mechanisms.     

TIME-INTENSITY PROPERTIES OF SWEET AND BITTER STIMULI: IMPLICATIONS FOR SWEET AND BITTER TASTE CHEMORECEPTION

Interindividual differences in sweet and bitter taste sensitivity were investigated using time-intensity (TI) measurements and multivariate statistics. TI profiles were obtained in triplicate from 25 subjects for 23 sweet and/or bitter stimuli first matched to be approximately equi-intense to 200 mM NaCl. Sweet stimuli, except for the larger sweeteners, were less persistent, and required less time to reach maximum intensity than bitter stimuli. The results of principal component (PCA) and cluster (CA) analyses of the stimuli X subjects matrices for maximum intensity (Imax), time to maximum intensity (Tmax), total duration (Tdur), and area under the curve (Area) suggest that sweet and bitter stimuli do not share common receptors; and that there are at least two receptor mechanisms each for sweet taste (one for sugars and other small compounds, and the other for large sweeteners) and bitter taste (one for PTC/PROP and one for other bitter compounds).     

Riboflavin-binding protein is a novel bitter inhibitor

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

RELATIONSHIPS BETWEEN BITTER TASTE SENSITIVITY AND CONSUMPTION OF BITTER SUBSTANCES

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

Effect of Ca2+, cyclic GMP, and cyclic AMP added to artificial solution perfusing lingual artery on frog gustatory nerve responses

The lingual artery of the bullfrog was perfused with artificial solution and the effects of Ca2+, Ca-channel blockers (MnCl2 and verapamil), cGMP, and cAMP added to the perfusing solution of the gustatory nerve responses were examined. The responses to chemical stimuli of group 1 (CaCl2, NaCl, distilled water, D-galactose, and L- threonine) applied to the tongue surface were greatly decreased by a decrease in Ca2+ concentration in the perfusing solution, suppressed by the Ca-channel blockers, enhanced by cGMP, and suppressed by cAMP. The responses to chemical stimuli of group 2 (quinine hydrochloride, theophylline, ethanol, and HCl) were practically not affected by a decrease in Ca2+ concentration, the Ca-channel blockers, cGMP, and cAMP. The responses to the stimuli of group 1 seem to be induced by Ca influx into a taste cell that is triggered by depolarization and modulated by the cyclic nucleotides in a taste cell. The responses to group 2 seem to be induced without accompanying Ca influx.