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Serotonin modulates voltage-dependent calcium current in Necturus taste cells.

Necturus taste buds contain two primary cell types: taste receptor cells and basal cells. Merkel-like basal cells are a subset of basal cells that form chemical synapses with taste receptor cells and with innervating nerve fibers. Although Merkel-like basal cells cannot interact directly with taste stimuli, recent studies have shown that Merkel-like basal cells contain serotonin (5-HT), which may be released onto taste receptor cells in response to taste stimulation. With the use of whole cell voltage clamp, we examined whether focal applications of 5-HT to isolated taste receptor cells affected voltage-activated calcium current (I(Ca)). Two different effects were observed. 5-HT at 100 microM increased I(Ca) in 33% of taste receptor cells, whereas it decreased I(Ca) in 67%. Both responses used a 5-HT receptor subtype with a pharmacological profile similar to that of the 5-HT1A receptor, but the potentiation and inhibition of I(Ca) by 5-HT were mediated by two different second-messenger cascades. The results indicate that functional subtypes of taste receptor cells, earlier defined only by their sensitivity to taste stimuli, may also be defined by their response to the neurotransmitter 5-HT and suggest that 5-HT released by Merkel-like basal cells could modulate taste receptor function.

Animals↗

Facial taste responses of the channel catfish to binary mixtures of amino acids.

We investigated the neural processing of binary gustatory mixtures of amino acids by the facial taste system of the channel catfish, Ictalurus punctatus. In vivo electrophysiological recordings indicated that the magnitude of both integrated and single-unit facial taste responses to binary mixtures of amino acids was greatest if the components bound to independent receptor sites. Facial taste responses were obtained from 32 multiunit and 55 single taste fiber preparations to binary mixtures of amino acids whose components bind to independent taste receptor sites (group I) or to the same or highly cross-reactive taste receptor sites (group II). All component stimuli were adjusted in concentration to provide approximately equal response magnitude as determined by either the height of the integrated multiunit taste response or by the number of action potentials generated/3 s of response time/single taste fiber. The mixture discrimination index (MDI), defined as the response to the mixture divided by the average of the responses to the component stimuli, was calculated for each test of a binary mixture. MDIs of group I binary mixtures for both the integrated multiunit and single fiber data were significantly greater than those for either the control or group II binary mixtures. In a subset of multiunit recordings, the MDIs of a group I binary mixture across three log units of stimulus concentration were similar and significantly greater than those of a group II binary mixture. Analysis of the single fiber data also indicated that the MDIs of group I binary mixtures were significantly larger than those of group II binary mixtures for both alanine-best and arginine-best taste fibers; however, the MDIs of group I binary mixtures calculated from recordings from arginine-best taste fibers were significantly greater than those recorded from alanine-best taste fibers.

Amino Acids↗

Embryonic taste buds develop in the absence of innervation.

It has been hypothesized that taste buds are induced by contact with developing cranial nerve fibers late in embryonic development, since descriptive studies indicate that during embryonic development taste cell differentiation occurs concomitantly with or slightly following the advent of innervation. However, experimental evidence delineating the role of innervation in taste bud development is sparse and equivocal. Using two complementary experimental approaches, we demonstrate that taste cells differentiate fully in the complete absence of innervation. When the presumptive oropharyngeal region was taken from a donor axolotl embryo, prior to its innervation and development of taste buds, and grafted ectopically on to the trunk of a host embryo, the graft developed well-differentiated taste buds. Although grafts were invaded by branches of local spinal nerves, these neurites were rarely found near ectopic taste cells. When the oropharyngeal region was raised in culture, numerous taste buds were generated in the complete absence of neural elements. Taste buds in grafts and in explants were identical to those found in situ both in terms of their morphology and their expression of calretinin and serotonin immunoreactivity. Our findings indicate that innervation is not necessary for complete differentiation of taste receptor cells. We propose that taste buds are either induced in response to signals from other tissues, such as the neural crest, or arise independently through intrinsic patterning of the local epithelium.

Ambystoma↗

Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds.

Leptin is a hormone that regulates food intake, energy expenditure and body weight. Our previous studies have demonstrated that the taste organ is a new peripheral target for leptin in mice. Leptin selectively inhibits the responses of taste nerves and receptor cells to sweet substances without affecting responses to sour, salty, and bitter substances. Still, there is no convincing evidence for the existence of leptin receptors (Ob-Rs) in taste receptor cells, especially the functional isoform Ob-Rb. We investigated the expression of 5 different Ob-R isoforms (a-e) and 6 STAT (signal transducers and activators of transcription) members in mouse taste cells. STATs are considered to be involved in the leptin signaling via Ob-Rb. Semiquantitative RT-PCR analysis showed that Ob-Rb was expressed in the taste buds of the fungiform and circumvallate papillae, but not so clearly in the surrounding epithelial tissue. The expression pattern among the three different tissues was similar to that of the taste cell specific G-protein, alpha-gustducin. The other Ob-R isoforms were widely detected in either the taste papillae or the epithelial tissue. Among 6 STAT members, STAT3 showed the highest relative abundance of mRNA in the taste buds. Consistently, in situ hybridization analysis showed that while Ob-Rb and STAT3 signals were detected in some taste bud cells, the signals were not clearly observed in the epithelial tissue cells. In conclusion, the present study provides evidence of the existence of the leptin receptor, Ob-Rb, and STAT3 in the mouse taste bud cells. This finding further confirms the involvement of leptin in the control of taste sensitivities to sweet substances in mice.

Animals↗

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.

Adult↗

[Taste disturbance after tonsillectomy].

There are some patients, though few in number, who complain of taste disturbance after tonsillectomy. Actual measurement of the distance between the lingual branch of the glossopharyngeal nerve, which controls taste in the posterior portion of the tongue, and the lower pole of the palatine tonsil, using a cadaver, showed the distance to be only 2-4 mm, thereby suggesting the danger of direct or indirect disturbance of this nerve by tonsillectomy. Among the 3,583 outpatients complaining of taste disturbance whom we have treated at our taste disorder clinic in the last 15 years, 11 (0.31%) were found to be suffering from taste disorder triggered by tonsillectomy. Among these 11 causes, the causes of taste disturbance have been identified in 8 cases. In three cases, the taste disturbance was caused by direct or indirect damage to the lingual branch of the glossopharyngeal nerve, whereas in another two cases, the disturbance was attributable to medication following tonsillectomy. In the remaining three cases, the diagnosis was a taste disturbance initiated by tonsillectomy but actually caused by a lack of dietary zinc. It is therefore important that patients be informed of the risk of post-operative taste disorder following tonsillectomy, at the time informed consent for tonsillectomy is obtained. It is equally important to measure the taste threshold values for each taste nerve and the serum zinc value as part of the pre-operational examination, and to ask the patients what drugs, if any, they take habitually.

Adult↗

Development of membrane properties in taste cells of fungiform papillae: functional evidence for early presence of amiloride-sensitive sodium channels.

Behavioral and physiological studies have demonstrated a reduced sensitivity to several taste stimuli early in development. It has been suggested that this reduced sensitivity results from a late maturation of underlying transduction mechanisms. Little is known, however, about maturation of membrane properties of taste cells early in development. We have obtained whole-cell recordings from single fungiform taste cells of rat pups to examine the development of the NaCl transduction system. Although taste buds undergo a considerable increase in size during development, membrane capacitance measurements revealed no change in membrane surface area of individual taste cells, suggesting that the increase in size results from an increase in the total number of cells per bud. Whole-cell recordings showed that taste cells from very young pups [postnatal day 2 (PND2)] already possessed voltage-activated Na+ and K+ currents with no apparent differences in size or kinetics compared with adults. Surprisingly, amiloride-sensitive Na+ responses, important for Na+ transduction, were found as early as PND2. The magnitude of responses to amiloride and the percentage of amiloride-sensitive cells remained the same throughout all age groups. Furthermore, the similarity of amiloride inhibition constants suggested that the channel in neonates is the same channel that is expressed in adult taste buds. Our results indicate that taste cells at PND2 already have acquired the transduction elements necessary for signaling NaCl responses to the afferent nerve. We hypothesize that complete functionality of the salt taste transduction system, however, may not be reached until amiloride-sensitive Na+ channels become selectively localized at the apical membrane. This would explain previous studies indicating that amiloride sensitivity cannot be detected before PND12 in the intact tongue. Apical clustering of channels along with the opening of the taste pore and an increase in the total number of taste cells per bud likely constitute additional important steps toward a fully functional sensory system.

Amiloride↗

Taste function in Sjögren's syndrome patients with special reference to clinical tests.

OBJECTIVE: We analyzed the correlation between taste functions and clinical features in patients with Sjögren's syndrome (SS). METHODS: Sixty-three patients were divided into two groups: group A consisting of patients with primary or secondary SS of the European classification, and group B consisting of non-SS complaining of dry eye and mouth. RESULTS: Eighteen percent of the group A patients and 11% of the group B patients complained of taste disorders. Electrogustometric examination detected taste disorders in 27% of the group A patients and 38% of the group B patients, while the filter paper disc method showed taste disorders in 30% of group A and 40% of group B. In group A, unstimulated and stimulated salivary flows were correlated with the ability to discriminate taste analyzed by the filter paper disc method, but not with the taste electrogustometric threshold. Serum zinc concentration was not significantly correlated with taste disorders in either group. CONCLUSION: Our findings showed that SS patients presented taste disorders less frequently than previously reported, and we speculated that taste disorder found in SS patients were due to the salivary flow deficiency that might prevent substances from reaching the taste buds.

Adult↗

Taste effects of lingual application of cardiovascular medications.

Medications used to treat cardiovascular diseases such as congestive heart failure, high blood pressure, and arrhythmia, are prescribed extensively in Western countries. However, taste complaints are common side effects of many of these cardiovascular medications. Although clinical observations are helpful in determining potential taste problems from a medication, experimental studies are necessary to obtain quantitative data on taste. In the studies performed here, nine cardiovascular medications (labetalol HCl, captopril, diltiazem HCl, enalapril maleate, hydrochlorothiazide, propranolol HCl, mexiletine HCl, procainamide HCl, and propafenone HCl) were applied to the tongue in human volunteers to measure the direct effect of these drugs on taste receptors. The medications were applied topically to the tongue surface of both young and elderly subjects to mimic the situation in which the drug is secreted into the saliva. Detection thresholds ranged from 0.048 mM (propafenone) to 0.438 mM (procainamide). The detection thresholds of healthy elderly subjects did not significantly differ from young controls. The compounds tested had a predominantly bitter taste with other qualities as well. In addition, topical application of the medications to the tongue affected the taste of one or more taste stimuli, with medications differing in the pattern of taste effects exhibited. The mechanism of taste effects is not fully known, but the results of this study suggest one route may be due to medications' effect on peripheral taste receptors.

Administration, Sublingual↗

Taste disorders in healthy "carriers" and "non-carriers" of Candida albicans and in patients with candidosis of the tongue.

Impairments in taste perception may be caused by a number of factors, including the presence of Candida albicans in the oral cavity. We attempted to establish whether the presence of Candida albicans on the tongue is a cause of taste disorders by studying taste disorders in patients with candidosis of the tongue and in healthy "carriers" and "non-carriers" of C. albicans. Taste disorders and their severity were objectively assessed by the filter-paper disk method in 18 patients with candidosis of the tongue and in 33 healthy "carriers" and 167 healthy "non-carriers" of C. albicans. The gustatory function was re-tested in 7 patients and 8 "carriers" after treatment with topical anti-mycotic medication to detect any improvement. Patients with candidosis of the tongue and "carriers" of C. albicans demonstrated significantly higher incidences (p<0.001) of taste disorders than did "non-carriers". The mean taste threshold of each of the four individual taste qualities was significantly higher in patients with candidosis than in "non-carriers". The average taste threshold was significantly higher in "carriers" than in "non-carriers". Post-treatment improvement or recovery from taste disorders was obtained in 5 out of 7 patients (71.4%) with candidosis and in 7 out of 8 "carriers" (87.5%) of C. albicans. This study clearly demonstrates that not only overt candidosis of the tongue but also commensal harboring of C. albicans is a cause of taste disorders.

Administration, Topical↗

[Analysis of saccharin and aspirin tasting ability among Mongolians of Xinjiang].

The saccharin and aspirin tasting abilities have been detected and analyzed in 710 individuals (328men, 382women) of Xinjiang Mongol. It is showed that the saccharin taste-blindness ratio among Mongolians was 4.648%,frequency of the recessive gene determining taste-blindness and the dominant gene determining taste ability was 0.2156, and 0.7844 respectively,and its mean testable threshold was 8.00+/-1.34 (0.108mol/L). Distribution of aspirin tasting threshold appeared a distinct curve with double peaks and single bottom,and demonstrated the aspirin tasting ability was a monogenic character. Solution NO.7 (3.00x10(-4)mol/L) at the bottom in the curve was the boundary of taste-blindness. The peak of taste-blindness was at the solution NO.1 (1.7x10(-2)mol/L), and the peak of tasters was at the solution NO.11 (1.25x10(-5)mol/L), The ratio of aspirin taste-blindness was 90.28%. The chi2 test has been used to evaluate the statistical difference in aspirin taste-blindness ratio between male and female, the result showed that there was no significant difference (P>0.90), and the gene determining for aspirin tasting ability located on autosomes.

English Abstract↗

Taste thresholds of patients with cancer of the esophagus.

Twelve patients with untreated cancer of the esophagus and 14 control subjects matched for age, smoking, and alcohol consumption were tested for taste thresholds. Taste acuity for the four basic tastes was evaluated by three stimulus forced choice techniques (Henkin). There were no significant differences between the groups for detection and recognition thresholds for sour, salty, sweet, or bitter taste stimuli. Comparison of patients' detection and recognition thresholds with those of eight young healthy nonsmokers showed marked differences. Salivary urea nitrogen concentration was not different between patients and matched controls and did not correlate with bitter taste thresholds. Variable results have been reported for taste sensitivity in patients with malignant disease. In view of the results of this study and the many factors which influence taste acuity, it appears that a general statement regarding taste alterations in cancer patients cannot be made. Choice of appropriate control groups to correct for factors known to affect taste but not related to cancer per se is important for proper interpretation of taste testing results.

Adult↗

Morphological and biochemical heterogeneity in facial and vagal nerve innervated taste buds of the channel catfish, Ictalurus punctatus.

In catfish, the facial nerve innervates taste buds distributed over the entire body including the barbels, while the glossopharyngeal and vagal nerves innervate oropharyngeal taste buds. Facial nerve innervated taste buds (FITBs) are thought to be involved in food detection and localization, while glossopharyngeal and vagal nerve innervated taste buds (VITBs) evaluate the palatability of food prior to ingestion. Physiological studies indicate that both oral and extra-oral taste buds detect sapid substances such as amino acids and nucleotides, but the facial taste system is more sensitive to some of these substances. The anatomical, molecular, and/or physiological mechanisms underlying the functional differences in these two gustatory pathways remain to be identified. In the current investigation we compare the basic morphological features of FITBs and VITBs and the distribution of the following metabolites: gamma-aminobutyric acid (GABA), glutamate, aspartate, alanine, taurine, and glutathione. Vagal innervated taste buds are significantly longer and narrower than FITBs, with fewer taste cells and a smaller nerve plexus. Each of the metabolites examined was heterogeneously distributed in taste cells with notably more GABA positive cells present in the VITBs. Patterns of metabolite colocalization suggest the presence of several taste cell subtypes. The morphological and metabolite differences noted between FITBs and VITBs provide a potential anatomical basis for the previously noted differences in physiological sensitivity.

Amino Acids↗

Taste performance in Sjogren's syndrome.

Sjogren's Syndrome (SS) patients have impaired salivary gland function and an elevated frequency of oral complaints. The taste complaints are thought to be due to sensory deficits that arise in the absence of sufficient saliva to maintain taste receptors. We assessed the subjective complaints, salivary production and taste functioning of SS patients and unaffected individuals. We found the expected decreased salivary gland function and increased frequency of taste complaints. Our taste assessment with weak stimuli confirmed and expanded the previous report of decreased taste threshold sensitivity in SS. However, perception of stronger taste stimuli was not impaired. In contrast with previous reports, patient judgments of intensity were not significantly reduced for any of the four taste qualities. Although the salivary gland function of all patients was markedly impaired relative to that of controls, patients lacking measurable salivary flow were no more likely than patients with residual function to exhibit subjective complaints or taste impairments. Our observations are inconsistent with a simple causal chain running from salivary gland dysfunction to sensory loss to taste complaints.

Adult↗

Radiotherapy-induced taste impairment.

Changes in taste perception occur in a significant proportion of cancer patients. Among cancer patients treated with radiotherapy (RT) in head and neck area, the vast majority reports an altered taste sense during and after treatments. Taste impairment starts a few weeks after the beginning of irradiation, and almost all such patients experienced loss of taste acuity at a dose of 60 Gy. Some studies investigated the four basic taste intensities (sweet, salty, sour and bitter) and the umami taste, and several of these reports identified diminished threshold sensitivity for at least one taste quality. Six months to one year after RT, taste acuity recovers to its previous level in many patients, but some patients show incomplete or no recovery even several years later. Taste impairment has profound effects on patients' quality of life because is associated with weight loss through reduced appetite and altered patterns of food intake. Damage to the major salivary glands during head and neck RT leads to disturbance in taste acuity. With the implementation of new radiation techniques, such as conformal and intensity-modulated RT in head and neck irradiation, the late-radiation effects can probably be reduced, but the remaining sequelae are still bothersome to the patients.

Head and Neck Neoplasms↗

Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways.

Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.

Action Potentials↗

Identification of sour-taste receptor genes.

Taste cells located in taste buds respond to gustatory stimuli using a complex arrangement of ion channels, receptor molecules and signaling cascades. Previous electrophysiological experiments have shown that sour taste (essentially a taste of protons) is mediated, at least in part, by apically located amiloride-sensitive channels in the rat. Here, the molecular cloning of sour-taste receptor genes is described. Using a combination of homology screening and functional expression approaches, we screened a rat circumvallate papilla cDNA library and identified acid-sensing ion channel-2a (ASIC2a) and ASIC2b, amiloride-sensitive proton-activated cation channels. In situ hybridization and reverse transcription-polymerase chain reaction experiments showed that ASIC2a and ASIC2b transcripts were localized in taste cells. Immunohistochemical and immunoprecipitation studies revealed that both channels were expressed in a subset of taste cells and that some of the cells expressed ASIC2a/ASIC2b heteromeric assemblies. Immunoelectron microscopic analyses demonstrated that some of the ASIC2a-immunopositive cells had the characteristics of type III cells, which make synaptic contacts with gustatory afferent neurons. According to our electrophysiological studies, stimulation by acetic acid generated larger inward currents in ASIC2a- or ASIC2a/ASIC2b-expressing oocytes than those induced by hydrochloric acid at the same proton concentration and these findings are in good agreement with the well-known taste phenomenon that acetic acid is more sour than hydrochloric acid at equal pH. Taken together, the present results strongly suggest that mucosal protons dissociated from sour-taste substances induce taste cell depolarization through the activation of the ASIC2a and ASIC2a/ASIC2b channels, which leads to transmitter release onto gustatory neurons.

Acid Sensing Ion Channels↗

A high-throughput screening procedure for identifying mice with aberrant taste and oromotor function.

Little is known about how specific genes influence taste function in mammals. One of the most promising ways to fill this void is to screen the progeny of chemically mutagenized (or genetically altered) mice for aberrant taste phenotypes and then identify the mutated gene(s) that is associated with each taste anomaly. To exploit this approach, a high-throughput and robust screening procedure is needed. We have attempted to meet this demand by developing an automated procedure that assesses taste responsiveness of individual mice to palatable and unpalatable taste stimuli. We focused on three taste stimuli (quinine hydrochloride, QHCl; sodium chloride, NaCl; and sucrose) and one mouse strain (C57BL/6). We used a commercially available gustometer system that both monitors the licking responses of mice and controls the presentation of each taste stimulus during successive 5 s trials. We describe a screening procedure that (after 2 days of simple training) can generate a concentration-response curve for NaCl or sucrose during a single 30 min test session, and for QHCl over three 30 min test sessions. A normative database based on the responses of 98 mice subjected to our screening procedure is also presented. We envision that investigators could use this normative database to assess taste function in the progeny of mutagenized (or genetically altered) mice. Any mouse that deviates significantly-e.g. three standard deviations (SD)-from the mean of the normative database would be flagged as having a potentially interesting mutation. We also developed an additional second screen for identifying mice with oromotor abnormalities. This latter screen is necessary because oromotor problems could lead to false positives or negatives in the screen for taste function, but is also useful for researchers interested in genes influencing oromotor circuitry. Throughout the development of the screening protocol, we sought to balance two conflicting demands: the need to maximize the screen's sensitivity and minimize its duration. This screen represents a significant improvement over the common two-bottle preference test because it assesses taste function more specifically and in a fraction of the time.

Animals↗