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Effect of tricyclic antidepressants on taste responses in humans and gerbils.

One of the side effects of antidepressant pharmacotherapy reported clinically is impairment of the sense of taste. In this study, the taste effects of four tricyclic antidepressant compounds (clomipramine HCl, desipramine HCl, doxepin HCl, and imipramine HCl) were evaluated experimentally by topical application of the drugs to the tongue. Taste detection threshold concentrations for all four medications ranged from 0.1 mM to 0.2 mM in young persons but were elevated by as much as 7.71 times that in elderly individuals who were taking no concurrent medications. Each compound had a predominantly bitter taste with other qualities including metallic, sour, and sharp-pungent. In addition, each tricyclic antidepressant at concentrations from 1 mM to 5 mM blocked responses to a wide range of taste stimuli in both humans and gerbils. The differential suppression of other tastes by tricyclic antidepressants at the level of the taste receptors may contribute to the clinical reports of dysgeusia and hypogeusia.

Adult↗

Mammalian sweet taste receptors.

The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery.

Animals↗

Thermal stimulation of taste.

The first electrophysiological recordings from animal and human taste nerves gave clear evidence of thermal sensitivity, and studies have shown that as many as half of the neurons in mammalian taste pathways respond to temperature. Because temperature has never been shown to induce sensations of taste, it has been assumed that thermal stimulation in the gustatory system is somehow nulled. Here we show that heating or cooling small areas of the tongue can in fact cause sensations of taste: warming the anterior edge of the tongue (chorda tympani nerve) from a cold temperature can evoke sweetness, whereas cooling can evoke sourness and/or saltiness. Thermal taste also occurs on the rear of the tongue (glossopharyngeal nerve), but the relationship between temperature and taste is different there than on the front of the tongue. These observations indicate the human gustatory system contains several different types of thermally sensitive neurons that normally contribute to the sensory code for taste.

Body Temperature↗

Taste changes in vitamin A deficiency.

Taste preferences were studied in two groups of rats depleted of vitamin A by dietary restriction. One group received sufficient vitamin A acid supplement to maintain normal growth. The other group was repleted with vitamin A alcohol after the classical deficiency symptoms had appeared; this group gradually lost normal preferences for NaCl and aversion to quinine solutions during depletion. Vitamin A alcohol repletion tended to restore taste preferences to normal. In contrast, the group receiving vitamin A acid showed normal taste preferences throughout the depletion period. When the vitamin A acid supplement was removed taste preferences became abnormal and returned to normal when vitamin A acid was restored. Peripheral gustatory neural activity of depleted rats without any form of vitamin A was less than normal both at rest and when the tongue was stimulated with NaCl solutions. Histological examination showed keratin infiltrating the pores of the taste buds. Accessory glandular tissues were atrophied and debris filled the trenches of the papillae. It is concluded that vitamin A acid can provide the vitamin A required for normal taste, as contrasted with its inability to maintain visual function. It is suggested that the effect of vitamin A is exerted at the receptor level, as a result of its role in the biosynthesis of mucopolysaccharides, which have been recently identified in the pore area of taste buds, as well as being present in the various secretions of the oral cavity.

Acetates↗

Taste responses to monosodium glutamate after alcohol exposure.

AIMS: The aim of the present study was to evaluate the effects of acute and chronic exposure to alcohol on taste responses to a prototypic umami substance, monosodium glutamate (MSG). METHODS: The rated intensity and pleasantness of MSG taste (0.03-10.0%) was compared in chronic male alcoholics (n = 35) and control subjects (n = 25). In a separate experiment, the effects of acute exposure of the oral mucosa to ethanol rinse (0.5-4.0%) on MSG taste (0.3-3.0%) were studied in 10 social drinkers. RESULTS: The alcoholic and control group did not differ in terms of the rated intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (P < 0.01) higher, i.e. worse, in the alcohol-dependent subjects. The difference remained significant after controlling for between-group differences in cigarette smoking and coffee drinking. Rinsing with ethanol did not alter either intensity or pleasantness of MSG taste in social drinkers. CONCLUSIONS: The present results suggest that: (i) neither acute nor chronic alcohol exposure modifies taste responses to MSG; (ii) alcohol dependence may be associated with deficit in threshold taste reactivity, as assessed by electrogustometry.

Adult↗

Genetic sensitivity to 6-n-propylthiouracil (PROP) and hedonic responses to bitter and sweet tastes.

Genetically mediated sensitivity to the bitter taste of 6-n-propylthiouracil (PROP) has been associated with greater acuity for bitter and for some sweet tastes. Thus far, few studies have explored the relationship between PROP taste sensitivity and hedonic responses to bitter and sweet. In this study, 87 normal-weight young women were divided into PROP non-tasters (n = 18), regular tasters (n = 49), and supertasters (n = 20), based on their PROP detection thresholds and the scaling of five suprathreshold solutions of PROP and NaCl. Non-tasters had thresholds > 1.8 x 10(-4) mol/l PROP. Supertasters had thresholds < 3.2 x 10(-5) mol/l PROP and PROP/NaCl ratios > 1.70. As expected, dislike of the bitter taste of PROP was determined by its perceived intensity, which was greater among supertasters than among regular tasters or non-tasters. Significant correlations were observed between PROP taste thresholds and the sum of intensity ratings (r = -0.61) and between summed intensity and summed hedonic ratings (r = -0.80). PROP taste sensitivity was weakly linked to enhanced perception of sweet taste, but did not predict hedonic responses to sucrose or to saccharin solutions. Given that the dislike of PROP solutions is determined by their perceived intensity, hedonic responses to PROP solutions may provide a rapid way of screening for PROP taster status.

Factor Analysis, Statistical↗

Discrimination between the tastes of sucrose and monosodium glutamate in rats.

Conditioned taste aversion studies have demonstrated that rats conditioned to avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of the sodium component of MSG taste, will generalize an aversion for MSG to sucrose and vice versa. This suggests that taste transduction for sodium, sucrose and MSG may intersect at some point. Generalization of conditioned taste aversion indicates that two substances share similar taste features, but it does not reveal the extent of their differences. In this study, we tested how well rats can discriminate sucrose and MSG under a variety of conditions. Water-deprived rats were trained on a combination of water reinforcement and shock avoidance to discriminate between MSG and sucrose, both with and without amiloride, and with and without equimolar NaCl in all solutions. In the absence of amiloride, rats reliably distinguished between MSG and sucrose down to 10 mM solutions. However, they could correctly identify solutions only above 50 mM in the presence of amiloride, equimolar sodium chloride, or both. These results suggest that gustatory stimulation by MSG and sucrose interact somewhere in taste transduction, perhaps within taste receptor cells or gustatory afferent pathways.

Amiloride↗

Expression of amiloride-sensitive epithelial sodium channels in mouse taste cells after chorda tympani nerve crush.

Our previous electrophysiological study demonstrated that amiloride-sensitive (AS) and -insensitive (AI) components of NaCl responses recovered differentially after the mouse chorda tympani (CT) was crushed. AI responses reappeared earlier (at 3 weeks after the nerve crush) than did AS ones (at 4 weeks). This and other results suggested that two salt-responsive systems were differentially and independently reformed after nerve crush. To investigate the molecular mechanisms of formation of the salt responsive systems, we examined expression patterns of three subunits (alpha, beta and gamma) of the amiloride-sensitive epithelial Na(+) channel (ENaC) in mouse taste cells after CT nerve crush by using in situ hybridization (ISH) analysis. The results showed that all three ENaC subunits, as well as alpha-gustducin, a marker of differentiated taste cells, were expressed in a subset of taste bud cells from an early stage (1-2 weeks) after nerve crush, although these taste buds were smaller and fewer in number than for control mice. At 3 weeks, the mean number of each ENaC subunit and alpha-gustducin mRNA-positive cells per taste bud reached the control level. Also, the size of taste buds became similar to those of the control mice at this time. Our previous electrophysiological study demonstrated that at 2 weeks no significant response of the nerve to chemical stimuli was observed. Thus ENaC subunits appear to be expressed prior to the reappearance of AI and AS neural responses after CT nerve crush. These results support the view that differentiation of taste cells into AS or AI cells is initiated prior to synapse formation.

Amiloride↗

Taste and aging.

Taste thresholds are known to rise with age, but the status of suprathreshold sensations is less clear. The present study assessed the perceived intensities of sodium chloride, sucrose, citric acid, and quinine hydrochloride with the method of magnitude matching. This method takes advantage of participants' ability to judge sensations from two sensory continua (in this case taste intensity and loudness) on a common intensity scale, in effect, matching them. Elderly and young adults matched most of the moderate and strong tastes to the same loudnesses. If the sounds were equivalently loud to elderly and young adults, then these results would mean that moderate and strong tastes were also equivalently strong, that is, taste sensation had not faded for our elderly adults. Water and dilute taste solutions were matched to louder sounds by elderly than young participants. This may reflect the presence of a mild dysgeusia (background taste).

Acoustic Stimulation↗

Amiloride-sensitive sodium currents in identified taste cells of the frog.

Sodium ions occurring in food are thought to be detected, at least in part, through specific amiloride-sensitive, sodium channels (ASSCs) localized in taste receptor cells. Cells within taste buds are morphologically heterogeneous, and include taste receptor cells and other cells that could perform a support or even transduction role. It is not known whether subsets of the taste bud cells express ASSCs, and whether the properties of these channels are similar. By applying the patch-clamp technique to morphologically distinct cells, the supporting wing cells, isolated from the frog taste disk, I have found functional ASSCs that are moderately sensitive to amiloride (Ki 3-4 microM) and which are distinctly lower in affinity for amiloride than reported frog taste receptor cells (Ki 0.2 microM). These results support the hypotheses of the existence of distinct, functional ASSCs in different cell morphotypes, at least in frog taste organs.

Amiloride↗

Optical recordings of taste responses from fungiform papillae of mouse in situ.

Single taste buds in mouse fungiform papillae consist of approximately 50 elongated cells (TBCs), where fewer than three TBCs have synaptic contacts with taste nerves. We investigated whether the non-innervated TBCs were chemosensitive using a voltage-sensitive dye, tetramethylrhodamine methyl ester (TMRM), under in situ optical recording conditions. Prior to the optical recordings, we investigated the magnitude and polarity of receptor potentials under in situ whole-cell clamp conditions. In response to 10 mM HCl, several TBCs were depolarized by approximately 25 mV and elicited action potentials, while other TBCs were hyperpolarized by approximately 12 mV. The TBCs eliciting hyperpolarizing receptor potentials also generated action potentials on electrical stimulation. A mixture of 100 mM NaCl, 10 mM HCl and 500 mM sucrose depolarized six TBCs and hyperpolarized another three TBCs out of 13 identified TBCs in a taste bud viewed by optical section. In an optical section of another taste bud, 1 M NaCl depolarized five TBCs and hyperpolarized another two TBCs out of 11 identified TBCs. The number of chemosensitive TBCs was much larger than the number of innervated TBCs in a taste bud, indicating the existence of chemosensitivity in non-innervated TBCs. There was a tendency for TBCs eliciting the same polarity of receptor potential to occur together in taste buds. We discuss the role of non-innervated TBCs in taste information processing.

Action Potentials↗

Molecular and physiological evidence for glutamate (umami) taste transduction via a G protein-coupled receptor.

Recent molecular analyses have demonstrated that a metabotropic glutamate receptor, mGluR4, is expressed in taste buds from rat circumvallate and foliate papillae. Behavioral studies demonstrated that L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist for mGluR4 and related receptors, mimics the taste of monosodium glutamate (MSG) in rats. mGluR4 is known to signal through inhibition of the cyclic adenosine-5',3'-monophosphate (cAMP) cascade. Circumvallate and foliate taste buds exhibit decreases of cAMP levels following stimulation with MSG, and the response is potentiated by 5'-inosine monophosphate, suggesting that it is related to umami taste. Further, experiments on mice with the mGluR4 gene knocked out support the interpretation that mGluR4 is a key component in glutamate taste. Glutamate may also stimulate taste buds through an ionotropic receptor pathway. In patch-clamp studies, glutamate evokes two types of currents, similar to those elicited by N-methyl-D-aspartate (NMDA) and L-AP4. We speculate upon the significance of two glutamate receptor pathways in taste buds.

Animals↗

Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships.

Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p = 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight loss experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p = 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.

Adult↗

Tastants evoke cAMP signal in taste buds that is independent of calcium signaling.

We previously showed that rat taste buds express several adenylyl cyclases (ACs) of which only AC8 is known to be stimulated by Ca2+. Here we demonstrate by direct measurements of cAMP levels that AC activity in taste buds is stimulated by treatments that elevate intracellular Ca2+. Specifically, 5 microM thapsigargin or 3 microM A-23187 (calcium ionophore), both of which increase intracellular Ca2+ concentration ([Ca2+]i), lead to a significant elevation of cAMP levels. This calcium stimulation of AC activity requires extracellular Ca2+, suggesting that it is dependent on Ca2+ entry rather than release from stores. With immunofluorescence microscopy, we show that the calcium-stimulated AC8 is principally expressed in taste cells that also express phospholipase Cbeta2 (i.e., cells that elevate [Ca2+]i in response to sweet, bitter, or umami stimuli). Taste transduction for sucrose is known to result in an elevation of both cAMP and calcium in taste buds. Thus we tested whether the cAMP increase in response to sucrose is a downstream consequence of calcium elevation. Even under conditions of depletion of stored and extracellular calcium, the cAMP response to sucrose stimulation persists in taste cells. The cAMP signal in response to monosodium glutamate stimulation is similarly unperturbed by calcium depletion. Our results suggest that tastant-evoked cAMP signals are not simply a secondary consequence of calcium modulation. Instead, cAMP and released Ca2+ may represent independent second messenger signals downstream of taste receptors.

Animals↗

Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides.

Current evidence points to the existence of multiple processes for bitter taste transduction. Previous work demonstrated involvement of the polyphosphoinositide system and an alpha-gustducin (Galpha(gust))-mediated stimulation of phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G protein gamma-subunit, Ggamma(13), colocalizes with Galpha(gust) and mediates the denatonium-stimulated production of inositol 1,4,5-trisphosphate (IP(3)). Using quench-flow techniques, we show here that the bitter stimuli, denatonium and strychnine, induce rapid (50-100 ms) and transient reductions in cAMP and cGMP and increases in IP(3) in murine taste tissue. This decrease of cyclic nucleotides is inhibited by Galpha(gust) antibodies, whereas the increase in IP(3) is not affected by antibodies to Galpha(gust). IP(3) production is inhibited by antibodies specific to phospholipase C-beta(2) (PLC-beta(2)), a PLC isoform known to be activated by Gbetagamma-subunits. Antibodies to PLC-beta(3) or to PLC-beta(4) were without effect. These data suggest a transduction mechanism for bitter taste involving the rapid and transient metabolism of dual second messenger systems, both mediated through a taste cell G protein, likely composed of Galpha(gust)/beta/gamma(13), with both systems being simultaneously activated in the same bitter-sensitive taste receptor cell.

Animals↗

Effects of electrical stimulation of the chorda tympani nerve on taste responses in the nucleus of the solitary tract.

Despite evidence for an abundance of inhibitory synaptic processes within the taste-responsive portion of the brain stem, little is known about how these processes are activated or modulated. In this context, this study tested the hypothesis that activation of the chorda tympani nerve (CT) invokes inhibition that influences gustatory neural information processing in the rostral nucleus of the solitary tract (NTS). Stimulating electrodes were implanted in the middle ear of urethane-anesthetized rats to enable the passage of current across the CT. Electrophysiological responses to sucrose, NaCl, HCl, and quinine were recorded from single NTS neurons both individually and immediately following tetanic electrical stimulation of the CT. Additionally, NTS field responses to paired pulse stimulation of the CT were recorded. Electrical pulses delivered to the CT were found to produce a compound action potential with four components. Taste-responsive units in the NTS showed tetanus-evoked responses that varied in latency and strength. Those cells that showed strong, short latency responses to CT stimulation showed large magnitude responses to NaCl and were relatively narrowly tuned. Units with longer latencies generally responded more broadly to taste stimuli and with lower response magnitudes. Following tetanus, taste responses in 20 (43%) of the 46 units were reversibly altered in a stimulus-selective manner. Taste responses in 18 units were both enhanced and attenuated following tetanic stimulation, although attenuation was much more common. Additionally, tetanus was found to affect the temporal organization of spikes within taste responses to one stimulus in seven units (15%), four of which also showed changes in response magnitude to a different stimulus following tetanus. The influence of tetanus on taste responses was shown to be reliable and repeatable in neurons from which stimulus trials were recorded more than once. Across all units, responses to quinine were most dramatically and frequently attenuated following tetanus, while those to NaCl were least susceptible to change. NTS field responses evoked by paired pulse stimulation of the CT suggested that the initial pulse evoked an inhibitory influence in the NTS that decayed and returned to baseline by 2 s. These data are consistent with the idea that afferent input to the NTS normally activates inhibitory synaptic activity. As with other sensory systems, such inhibition may serve to facilitate contrast in the neural representation of different stimulus qualities.

Action Potentials↗

Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus in rats.

Extracellular action potentials were recorded from 73 neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of anesthetized Wistar rats during gustatory, thermal, and tactile stimulation of the whole oral cavity. The stimulus array consisted of 16 room-temperature (23 degrees C) sapid stimuli, distilled water at three temperatures (0, 23, and 37 degrees C), and 0.1 M NaCl at three temperatures (0, 23, and 37 degrees C). Among all 151 neurons isolated in VPMpc, 9% responded exclusively to taste, 33% to taste and temperature, none to taste and touch, but 6% to all three modalities. Discharge rates evoked by the basic tastants were 13.8 +/- 1.6 (SD) spikes/s for 0.1 M NaCl, 9.3 +/- 1.4 spikes/s for 0.01 M HCl, 5.1 +/- 0.9 spikes/s for 0.5 M sucrose, and 4.3 +/- 0.6 spikes/s for 0.01 M quinine HCl. Water evoked mean responses at 0, 23, and 37 degrees C of 9.9 +/- 1.5, 0.6 +/- 0.4, and 1.3 +/- 0.9 spikes/s, respectively. The mean firing rate evoked by 37 and 0 degrees C NaCl was 15.0 +/- 2.4 and 17.0 +/- 2.8 spikes/s, respectively. The exponent of the NaCl concentration-response power function was 0.39. Thalamic taste cells were broadly tuned. The mean breadth-of-tuning coefficient for these 73 gustatory cells was 0.79 +/- 0.02. Two cells responded predominantly with inhibition, which accounted for the majority of inhibitory responses. The taste neurons were statistically divisible into three groups: sodium-oriented (n = 40), acid-oriented (n = 12), and sugar-oriented (n = 17). Four additional bitter-oriented neurons were not closely enough related to be defined as a group and were considered outliers. The sodium-oriented group could be divided into three statistically distinct subgroups, differing in the specificity of their responses to NaCl. With respect to polymodal sensitivity, spontaneous rate, evoked response rates, signal-to-noise ratio, proportions of cells responding best to basic tastants, taste neuron groups, taste spaces, and temporal responses, VPMpc neurons have characteristics that are intermediate between those of parabrachial and cortical gustatory neurons.

Action Potentials↗

Ca(2+)-dependent Cl- conductance in taste cells from Necturus.

1. Taste responses adapt to a constant chemical stimulus. The present study describes a new ionic conductance in taste cells--a Ca(2+)-dependent anion conductance that may explain taste adaptation. 2. Patch-clamp recordings were made on isolated Necturus taste cells or on taste cells in lingual slices. When Na+ and K+ currents were eliminated with tetrodotoxin (TTX) and tetraethyl-ammonium (TEA) in the bath and replacing K+ with N-methyl-D-glucamine (NMDG+) in the pipette, Ca2+ currents were followed by prolonged outward currents. Outward current was abolished when Ca2+ was substituted with Ba2+ or when Cl- was replaced with large organic anions (methanesulfonate, isethionate, or ascorbate). 3. The outward, Ca-dependent current was reduced by certain agents that block Cl- conductances in other tissues, namely 4-acet-amido-4-isothiocyanostilbene-2,2-disulfonic acid (SITS) and 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS). However, other Cl- channel blockers--9-AC, furosemide and an antibody to Cl channels-had little or no specific effect on the Ca-dependent outward current in Necturus taste cells. 4. We postulate that the biological action of this Ca-dependent anion conductance in situ is to terminate depolarizing receptor potentials, even during maintained chemostimulation, thereby playing an important role in chemosensory adaptation and modulation of impulse discharge patterns in taste buds.

Afferent Pathways↗