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Electron microscopic observation of vallate taste buds of zinc-deficient rats with taste disturbance.

Henkin et al. (1975) reported that there is a loss of the dense substance in the taste pore region, a loss of microvilli and a decrease of dark granules and microvacuolation in the taste pore buds of patients who complain of taste disturbance. In our experiment, we prepared artificially zinc-deficient rats by feeding a zinc-deficient diet and observed the same results in the taste buds of zinc-deficient rats with taste disturbance.

Animals↗

A candidate taste receptor gene near a sweet taste locus.

The mechanisms underlying sweet taste in mammals have been elusive. Although numerous studies have implicated G proteins in sweet taste detection, the expected G protein-coupled receptors have not been found. Here we describe a candidate taste receptor gene, T1r3, that is located at or near the mouse Sac locus, a genetic locus that controls the detection of certain sweet tastants. T1R3 differs in amino acid sequence in mouse strains with different Sac phenotypes ('tasters' versus 'nontasters'). In addition, a perfect correlation exists between two different T1r3 alleles and Sac phenotypes in recombinant inbred mouse strains. The T1r3 gene is expressed in a subset of taste cells in circumvallate, foliate and fungiform taste papillae. In circumvallate and foliate papillae, most T1r3-expressing cells also express a gene encoding a related receptor, T1R2, raising the possibility that these cells recognize more than one ligand, or that the two receptors function as heterodimers.

Alleles↗

Biochemical studies of taste sensation: monoclonal antibody against L-alanine binding activity of catfish taste epithelium.

The L-alanine taste receptors of the channel catfish Ictalurus punctatus provide a useful biochemical model for studying taste receptor mechanisms. Mouse hybridomas that synthesize monoclonal antibodies have been produced. The antigen used to activate mouse spleen cells was the plasma membrane fraction obtained from the taste receptor-containing epithelium of the channel catfish. The spleen cells were fused with myeloma cells, Sp2/0-Ag14, to form hybridomas. To demonstrate inhibition of ligand binding by the product of these hybridomas, a catfish membrane fraction (fraction P2) was incubated with the antibody-containing preparation prior to assaying for L-[3H]alanine binding activity. We thereby demonstrated inhibition of binding of the taste ligand L-alanine to fraction P2. This approach should prove useful in further studies of receptor binding and transduction events in taste receptors.

Alanine↗

Human taste: response and taste bud number in fungiform papillae.

The number of basic taste qualities registered by single human fungiform papillae is correlated with the number of taste buds borne on these papillae. Multiple sensitivity was demonstrated both in single fungiform papillae and in single taste buds, with response to all four of the basic taste qualities occuring in a single taste bud.

Adolescent↗

Clinical evaluation of taste dysfunction using a salt-impregnated taste strip.

We have used special tests to investigate taste function in detail. To evaluate acuity for a salty taste, we used a paper with salt crystals, Salsave. The procedure is simple and takes only a few minutes. We analyzed the relationships between the magnitude of the threshold of response to this test and the results of other taste function tests in 126 patients who visited our clinic. The mean magnitude of the response to Salsave significantly correlated with the results of other taste tests. Thus, this is a useful method for screening the detection and recognition threshold of a salty taste.

Adult↗

Long-term effects of surgical desalivation upon taste acuity, fluid intake, and taste buds in the rat.

Taste bud structure and taste preferences in intact and desalivated animals were evaluated to ascertain whether there was a structure-function relationship. Thirty-three totally desalivated rats and 30 sham-operated controls were tested between 95 and 110 d after surgery with a 48-hour two-bottle preference paradigm; they were then sacrificed, and the tongue epithelium and circumvallate papillae taste buds were examined histologically. Desalivated rats manifested significantly increased preferences for normally avoided solutions. Histological study of the dorsal tongue epithelium revealed increased keratosis. There were qualitative changes in the taste buds of the circumvallate papillae with some taste buds appearing shrunken and disorganized.

Animals↗

Reduction of electrical coupling between Necturus taste receptor cells, a possible role in acid taste.

Cytoplasmic acidification in taste receptor cells is thought to be involved, at least in part, in acid taste transduction. Since in taste buds about 20% of the receptor cells are electrically coupled, we have tested whether reduction in intracellular pH affects these lateral synaptic interactions. By applying the patch clamp technique to a slice preparation of Necturus lingual epithelium, we found that electrical coupling between taste receptor cells was strongly reduced by cytoplasmic acidification. Therefore, electrical coupling in taste buds might be modified during acid stimulation.

Acids↗

Taste avoidance induced by wheel running: effects of backward pairings and robustness of conditioned taste aversion.

Rats repeatedly exposed to a distinctive novel solution (conditioned stimulus, CS) followed by the opportunity to run in a wheel subsequently drink less of this solution. Investigations on this phenomenon indicate that wheel running is an effective unconditioned stimulus (US) for establishing conditioned taste aversion (CTA) when using a forward conditioning procedure (i.e., the US-wheel running follows the CS-taste). However, other studies show that wheel running produces reliable preference for a distinctive place when pairings are backward (i.e., the CS-location follows the US-wheel running). One possibility to account for these results is that rewarding aftereffects of wheel running conditioned preference to the CS. The main objective of the present study was to assess the effects of backward conditioning using wheel running as the US and a distinctive taste as the CS. In a between-groups design, two experimental groups [i.e., forward (FC) and backward conditioning (BC)] and two control groups [CS-taste alone (TA) and CS-US unpaired (UNP)] were compared. Results from this experiment indicated that there is less suppression of drinking when a CS-taste followed a bout of wheel running. In fact, rats in the BC group drank more of the paired solution than all the other groups.

Animals↗

Taste agnosia following gustatory neocortex ablation: dissociation from odor and generality across taste qualities.

In Experiment 1, rats trained to avoid drinking in the presence of a compound odor (benzyl acetate) and taste (sucrose) conditional stimulus (CS) lost the taste habit but retained the odor habit following gustatory neocortex (GN) ablation. Conversely, olfactory bulb ablation resulted in loss of the odor habit but retention of the taste habit. In Experiment 2, rats lacking GN did not retain preoperatively instated learned aversions to a suprathreshold quinine hydrochloride (bitter) taste solution which had been employed as a CS. However, rats with GN lesions that were virtually identical to those of the bitter-trained group retained a preoperatively learned aversion to a hydrochloric acid (sour) CS. Experiment 3 demonstrated that reliable agnosia for an acid CS could be produced by lesions that extended more deeply into perirhinal areas near the claustrum at the level of the GN. It is concluded that the agnosia following GN ablation is relatively specific to gustation and that agnosia for preoperatively acquired taste aversion habits occurs for all four basic gustatory stimuli following anterolateral cortex ablations centered on the GN.

Agnosia↗

Novel tastes elevate c-fos expression in the central amygdala and insular cortex: implication for taste aversion learning.

Taste novelty strongly modulates the speed and strength of taste aversion conditioning. To identify molecular signals responsive to novel tastes, immunostaining for c-fos protein (Fos-like immunoreactivity [FLI]) was used to mark neurons that responded differentially to taste novelty. Novel saccharin induced larger increases in FLI than familiar saccharin. This pattern was seen in central amygdala and insular cortex, but not in basolateral amygdala, parabrachial nucleus, or nucleus of the solitary tract. Other parameters known to influence aversion learning were tested for effects on FLI. Manipulations known to reduce the strength of learning blunted the FLI response, supporting the idea that FLI marks neural pathways critical to taste processing during acquisition, and that c-fos expression is a key transcriptional event underlying this plasticity.

Amygdala↗

Temporal changes in NCAM immunoreactivity during taste cell differentiation and cell lineage relationships in taste buds.

Neural cell adhesion molecule (NCAM) is a type III cell marker in the taste buds. In order to clarify the cell type of Mash1-expressing cells in taste buds, expression of NCAM was examined in Mash1-expressing taste cells of adult mice in comparison with gustducin- and T1r3-expressing cells, using a combination of NCAM immunohistochemistry and in situ hybridization. About 98% of Mash1-expressing cells were NCAM immunopositive (IP), suggesting that Mash1-expressing cells should be categorized as type III cells. Unexpectedly, small subsets of gustducin- and T1r3-expressing cells were also found to be NCAM-IP, contradicting previous immunohistochemical studies in rats, in which gustducin-IP cells were observed specifically in type II cells, which do not have NCAM immunoreactivity. Examinations of developing taste buds showed temporal changes in the ratio of NCAM-IP cells in gustducin- and T1r3-expressing cells; the ratio of NCAM-IP cells in these gene-expressing cells were approximately 90% at 0.5 days after birth and decreased markedly during development. In contrast, the majority of Mash1-expressing cells showed constant NCAM immunoreactivity throughout development. In addition, BrdU-labeling experiments showed that the differentiation of Mash1-expressing cells precedes those of gustducin- and T1r3-expressing cells in taste buds of adult mice. These results suggest that T1r3- and gustducin-expressing cells are NCAM-IP at the beginning of cell differentiation, and that NCAM immunoreactivity in gustducin- and T1r3-expressing cells might remain from the previous developmental stage expressing Mash1.

Animals↗

Neoculin, a taste-modifying protein, is recognized by human sweet taste receptor.

Neoculin, a sweet protein occurring in Curculigo latifolia, is unique in that it also has taste-modifying activity capable of converting sourness to sweetness. Calcium imaging analysis with HEK cells expressing the human sweet taste receptor, hT1R2/T1R3 demonstrated that the intracellular calcium concentration increased following the addition of 20 microM neoculin. The use of lactisole, a blocker of hT1R3, inhibited the intracellular calcium concentration increase almost completely. In sensory tests, when acetate buffers with different pH values were placed on the tongue after tasting neoculin, a higher intensity of sweetness was detected at lower pH. The sweetness was also suppressed with the addition of lactisole. These results suggest that both the sweetness and the taste-modifying activity are mediated via the human sweet taste receptor.

Benzene Derivatives↗

Terbinafine-associated taste disturbance with normal taste threshold scores.

The medical literature reveals numerous reports of transient taste disturbance associated with the use of oral terbinafine. A review of these reports, however, fails to confirm taste disturbances by formal taste testing. In this article, a case of long-standing taste dysfunction in a patient who exhibited normal formal taste thresholds is described.

Administration, Oral↗

Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center.

Smell and taste disorders are common in the general population, yet little is known about their nature or cause. This article describes a study of 750 patients with complaints of abnormal smell or taste perception from the University of Pennsylvania Smell and Taste Center, Philadelphia. Major findings suggest that: chemosensory dysfunction influences quality of life; complaints of taste loss usually reflect loss of smell function; upper respiratory infection, head trauma, and chronic nasal and paranasal sinus disease are the most common causes of the diminution of the sense of smell, with head trauma having the greatest loss; depression frequently accompanies chemosensory distortion; low body weight accompanies burning mouth syndrome; estrogens protect against loss of the sense of smell in postmenopausal women; zinc therapy may provide no benefit to patients with chemosensory dysfunction; and thyroid hormone function is associated with oral sensory distortion. The findings are discussed in relation to management of patients with chemosensory disturbances.

Burning Mouth Syndrome↗

Zinc deficiency and taste dysfunction; contribution of carbonic anhydrase, a zinc-metalloenzyme, to normal taste sensation.

The present study was designed to clarify the effect of zinc deficiency on sodium chloride preference, the lingual trigeminal and taste nerves transduction, and carbonic anhydrase (CA) activity of the tongue surface and salivary gland. Male SD rats, 4 weeks old, were divided into four groups, and fed zinc-deficient (Zn-Def), low-zinc (Low-Zn), and zinc-sufficient diets with free access (Zn-Suf) and pair-feeding (Pair-fed). After taking part in the preference tests for 42 days, the rats were provided for the chorda tympani and lingual trigeminal nerves recordings, then finally sacrificed and the tongue and submandibular gland excised to measure CA activity. Sodium chloride preference increased only after 4 days of the feeding of zinc-deficient and low-zinc diets, which means that the taste abnormality appears abruptly in zinc deficieny and even though in marginal zinc deficiency. Reduced CA activities of the taste-related tissues in zinc-deficient group paralleled well with the decreased taste and lingual trigeminal nerves sensitivities.

Animals↗

c-Fos induction in response to taste stimuli previously paired with amphetamine or LiCl during taste aversion learning.

Amphetamine and lithium chloride (LiCl) are both effective unconditioned stimuli (USs) in the establishment of conditioned taste aversions (CTA) in the rat. However, the mechanism of action of these drugs is quite different with the area postrema and related emetic circuitry critical to the response to LiCl but not amphetamine. c-Fos immunohistochemistry was used to define brain regions activated during drug administration and during expression of a CTA using either amphetamine or LiCl as the US drug. Administration of LiCl induced dense c-Fos-like immunoreactivity (c-FLI) in the nucleus of the solitary tract (NTS) while amphetamine induced only light staining in this area. A conditioned stimulus (CS) saccharin solution paired with amphetamine, however, was associated with c-FLI in NTS in a pattern quite similar to that seen to a LiCl-paired CS. This suggests that the pattern of c-Fos expression to a taste CS after conditioning is characteristic of aversion conditioning, in general, and appears not to represent a matching of the conditioned response to specific unconditioned effects of the drug. To examine this conditioned response further, c-FLI to the aversive saccharin CS was compared to the response to quinine hydrochloride, which is innately aversive. Although behaviorally the animals' ingestive responses were quite similar, the saccharin CS induced significant elevations of c-FLI in NTS whereas the quinine did not. Thus, a taste which had become aversive by virtue of conditioning induced c-FLI expression in NTS while a taste which was inherently aversive did not.

Amphetamine↗

Deficient dietary intake of vitamin E in patients with taste and smell dysfunctions: is vitamin E a cofactor in taste bud and olfactory epithelium apoptosis and in stem cell maturation and development?

OBJECTIVES: We reviewed dietary intake of several nutrients in a large group of patients with taste and smell dysfunction, compared intake of these nutrients with standard values, and recognized that intake of vitamin E was significantly less than that of most other nutrients. Based on this observation we attempted to develop an hypothesis of the possible role vitamin E might play in these sensory disorders. METHODS: Vitamin E intake was measured in 250 patients with taste and smell dysfunctions. RESULTS: Intake of the vitamin was 3.2 +/- 0.2 mg/d (mean +/- standard error of the mean), or 36 +/- 2% of the recommended daily allowance, an intake significantly below that considered adequate. This diminished intake occurred with normal intake of total calories; protein; fat; carbohydrate; several vitamins, including thiamin, niacin, and pyridoxine; and the trace metals zinc, copper, and iron. CONCLUSIONS: Although specific relations between vitamin E intake and smell and taste dysfunctions are unclear, the non-antioxidant roles of vitamin E indicate that it is a factor in apoptosis, cellular signaling, and growth of various cell lines, suggesting that this vitamin may play a role in growth and development of stem cells in taste buds and olfactory epithelium.

Adolescent↗

Primary culture of rat taste bud cells that retain molecular markers for taste buds and permit functional expression of foreign genes.

Taste buds are constituted of several kinds of cells which have distinct characteristics and play different roles. In this study, we have established an in vitro culture system by optimizing the method for isolating the cells and by selecting culture media and reagents effective for cell viability and adhesion. As a result, the taste bud cells were adhesive and viable for over 3 days when cultured onto Matrigel-coated dishes in medium based on keratinocyte growth medium. The cells retained molecular markers for both the cytoskeleton and intracellular signaling such as cytokeratin 8 and phospholipase Cbeta2. In addition, three intracellular signaling molecules, gustducin, phospholipase Cbeta2, and inositol 1,4,5-trisphosphate receptor type 3, are expressed in the same correlation as those in vivo, although the ratio of signaling molecule-positive cells vs. total cells was somewhat lower in the culture than in vivo. Next, we tried several methods to introduce foreign genes into the cells, and obtained a greater than 90% efficiency of introduction using an adenovirus vector. Finally, we show that an exogenously expressed myc-tagged alpha1A-adrenoceptor sorts into the plasma membrane, and transduces a ligand-dependent signal resulting in intracellular [Ca(2+)] increase in about half of the infected cells. These results suggest that taste bud cells after 3 days of culture retain characteristic molecular markers, and may prove useful for describing the molecular and physiological features of taste bud cells, and that these cells can be further manipulated by adenovirus-mediated gene introduction.

Animals↗