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PubMed1993

Gustducin and transducin: a tale of two G proteins.

In the vertebrate taste cell, heterotrimeric guanine nucleotide-binding proteins (G proteins) are involved in the transduction of both bitter and sweet taste stimulants. The bitter compound denatonium raises the intracellular Ca2+ concentration in rat taste cells, apparently via G protein-mediated increases in inositol trisphosphate. Sucrose causes a G protein-dependent generation of cAMP in rat taste bud membranes; elevation of cAMP levels leads to taste cell depolarization. To identify and characterize those proteins involved in the taste transduction process, we have cloned G protein alpha subunit (G alpha) cDNAs from rat taste cells. Using degenerate primers corresponding to conserved regions of G proteins, we used the polymerase chain reaction to amplify and clone taste cell G alpha cDNAs. Eight distinct G alpha cDNAs were isolated, cloned and sequenced from a taste cell library. Among these clones was alpha gustducin, a novel taste G alpha closely related to the transducins. In addition to alpha gustducin, we cloned rod and cone transducins from taste cells. This is the first identification of transducin expression outside photoreceptor cells. The primary sequence of alpha gustducin shows similarities to the transducins in the receptor interaction domain and the phosphodiesterase activation site. These sequence similarities suggest that gustducin and transducin regulate taste cell phosphodiesterase, probably in bitter taste transduction.

Animals↗
PubMed1988

Sugar-activated ion transport in canine lingual epithelium. Implications for sugar taste transduction.

There is good evidence indicating that ion-transport pathways in the apical regions of lingual epithelial cells, including taste bud cells, may play a role in salt taste reception. In this article, we present evidence that, in the case of the dog, there also exists a sugar-activated ion-transport pathway that is linked to sugar taste transduction. Evidence was drawn from two parallel lines of experiments: (a) ion-transport studies on the isolated canine lingual epithelium, and (b) recordings from the canine chorda tympani. The results in vitro showed that both mono- and disaccharides in the mucosal bath stimulate a dose-dependent increase in the short-circuit current over the concentration range coincident with mammalian sugar taste responses. Transepithelial current evoked by glucose, fructose, or sucrose in either 30 mM NaCl or in Krebs-Henseleit buffer (K-H) was partially blocked by amiloride. Among current carriers activated by saccharides, the current response was greater with Na than with K. Ion flux measurements in K-H during stimulation with 3-O-methylglucose showed that the sugar-evoked current was due to an increase in the Na influx. Ouabain or amiloride reduced the sugar-evoked Na influx without effect on sugar transport as measured with tritiated 3-O-methylglucose. Amiloride inhibited the canine chorda tympani response to 0.5 M NaCl by 70-80% and the response to 0.5 M KCl by approximately 40%. This agreed with the percent inhibition by amiloride of the short-circuit current supported in vitro by NaCl and KCl. Amiloride also partially inhibited the chorda tympani responses to sucrose and to fructose. The results indicate that in the dog: (a) the ion transporter subserving Na taste also subserves part of the response to K, and (b) a sugar-activated, Na-preferring ion-transport system is one mechanism mediating sugar taste transduction. Results in the literature indicate a similar sweet taste mechanism for humans.

Amiloride↗
PubMed1993

Protein analysis of human von Ebner saliva and a method for its collection from the foliate papillae.

The lingual serous glands of von Ebner are located close to the foliate and circumvallate papillae. Saliva secreted by these glands provides the immediate environment of the taste buds, and it has been hypothesized that it modulates taste perception. The purpose of this study was to develop a technique for collection of unstimulated and stimulated saliva from human von Ebner glands. Saliva was collected under resting conditions and after application of various gustatory stimuli (sweet, sour, salt, and bitter) by insertion of periostrips into the folds of the foliate papillae of healthy human volunteers. Stimulated saliva was also collected in glass microcapillaries or micropipettes. The flow-rates of unstimulated von Ebner saliva were 2.3 +/- 0.6 (S.E.) microL/min and 4.5 +/- 1.2 (S.E.) microL/min with 1% citric acid stimulation. The protein content was 2.5 +/- 0.5 (S.E.) mg/mL. The SDS gel electrophoretic profile of von Ebner saliva revealed two protein bands of Mr 18,000 that were identified on Western blots as von Ebner gland (VEG) proteins. Although lingual lipase activity was detected at very low levels by enzyme assay, this protein was not detected on Western blots. This collection technique should prove useful for analysis of specific functions associated with secretion from von Ebner glands.

Age Factors↗
PubMed1996

Supertasting, earaches and head injury: genetics and pathology alter our taste worlds.

Family studies using thresholds showed that PROP (6-n-propylthiouracil) tasting is produced by a dominant allele, T. Nontasters have two recessive alleles and tasters have one or two dominant alleles. The bitterness of suprathreshold PROP and anatomical criteria subdivide tasters into medium and supertasters. Supertasters may be TT tasters, but this has yet to be demonstrated. Supertasters preceive the greatest bitterness and sweetness from many stimuli as well as the greatest oral burn from alcohol and capsaicin. Women are more likely than men to be supertasters. Otitis media and head trauma can alter taste and thus PROP classifications, complicating studies on PROP genetics. Some subjects with a history of otitis media show taste reductions, but others show enhanced tastes and appear to have more taste buds per fungiform papilla. Subjects with head trauma show reduced tastes on some oral loci, but there is evidence that severe reductions on the front of the tongue ameliorate reductions at the circumvallate papillae on the back of the tongue by a release of inhibition mechanism.

Brain Injuries↗
PubMed1994

Oral anatomy and tissue types.

The gross and microscopic anatomy of the oral cavity and its contents are discussed from the perspective of their function. Histologically, the oral mucosa is classified into three categories, lining, masticatory, and specialized. The epithelium of the lining mucosa is nonkeratinized stratified squamous, whereas that of the masticatory mucosa is ortho- or parakeratinized, to protect it from the shearing forces of mastication. Specialized mucosa possesses taste buds, small epithelially derived structures responsible for the perception of taste sensation. The subepithelial connective tissue of the lining and masticatory mucosae interdigitate with their epithelia, and the degree of interdigitations is directly correlated with the strength of the shearing forces acting on the mucosa. The oral mucosa also participates in the immunological defense of the oral cavity due to the presence of Langerhans cells, antigen presenting cells in the epithelium.

Connective Tissue↗
PubMed1981

Bar synapses in the end buds of lamprey skin.

The end buds of lamprey epidermis have been considered to be similar to taste buds, but the synapses on the receptor cells are of the type with a dense mass surrounded by lucent vesicles, which is not found in gustatory cells. It is suggested that the end buds may belong to the lateralis sensory system and be involved in the light sensitivity of lamprey skin.

Animals↗
PubMed2006

Bone morphogenetic proteins and noggin: inhibiting and inducing fungiform taste papilla development.

Fungiform papillae are epithelial specializations that develop in a linear pattern on the anterior mammalian tongue and differentiate to eventually contain taste buds. Little is known about morphogenetic and pattern regulation of these crucial taste organs. We used embryonic rat tongue, organ cultures to test roles for bone morphogenetic proteins, BMP2, 4 and 7, and antagonists noggin and follistatin, in development of papillae from a stage before morphological initiation (E13) or from a stage after the pre-papilla placodes have formed (E14). BMPs and noggin proteins become progressively restricted to papilla locations during tongue development. In E13 cultures, exogenous BMPs or noggin induce increased numbers of fungiform papillae, in a concentration-dependent manner, compared to standard tongue cultures; BMPs, but not noggin, lead to a decreased tongue size at this stage. In E14 cultures, however, exogenous BMP2, 4 or 7 each inhibits papilla formation so that there is a decrease in papilla number. Noggin substantially increases number of papillae in E14 cultures. Using beads for a highly localized protein delivery, papillae are inhibited in the surround of BMP-soaked beads and induced in large clusters around noggin-soaked beads. Follistatin, presented in culture medium or by bead, does not alter papilla formation or number. In all fungiform papillae that form under various culture conditions, the molecular marker, sonic hedgehog, is within each papilla. However, the BMP inhibitory effect on papillae is not prevented by disrupting sonic hedgehog signaling through addition of cyclopamine to cultures. BMPs and noggin alter cell proliferation in tongue epithelium in opposite ways, demonstrated with Ki67 immunostaining. We propose that the BMPs and noggin, colocalized within papilla placodes and the fungiform papillae per se, have opposing inhibitory and activating or inducing roles in papilla development in linear patterns. We present a model for these effects.

Animals↗
PubMed1994

Expression and localization of amiloride-sensitive sodium channel indicate a role for non-taste cells in taste perception.

Salty taste is blocked by the diuretic amiloride, which inhibits specific sodium channels. We have isolated an amiloride-sensitive sodium channel (ASSC) from taste tissues by polymerase chain reaction and screening of a cDNA library prepared from rat circumvallate papillae. Northern analysis reveals ASSC in taste and non-taste tissues with the highest level of expression of ASSC in the lung. In situ hybridization establishes ASSC localizations in the epithelia of lung and colon as well as tongue epithelial layers containing and lacking taste buds. These results support a model in which ASSC in non-taste cells regulates responses of taste cells to salt as well as other tastants.

Amiloride↗
PubMed2002

Course of recovery from taste receptor disturbance.

The course of recovery from taste receptor disturbance was studied in 119 patients with moderate-to-severe taste receptor disturbance that was cured or improved with zinc therapy. Taste receptor disturbance was idiopathic in 45 patients, drug-induced in 38 and due to zinc deficiency in 36. Recovery of taste, evaluated by filter paper disk testing and electrogustometry, followed 1 of 3 patterns: (i) in 54 (45.4%) of the 119 cases, taste improved simultaneously in the anterior (innervated by the chorda tympani nerve) and posterior (innervated by the glossopharyngeal nerve) portions of the tongue; (ii) in 53 (44.5%) of the cases, taste improved in the posterior portion first; and (iii) in 12 (10.1%) of the cases, taste improved in the anterior portion first. Zinc therapy was more effective in patients with the "posterior" pattern of recovery, and these patients also recovered the ability to sense sweet and bitter tastes earlier than other tastes. These results indicate that recovery of taste begins on the posterior portion of the tongue, which has an abundance of taste buds. The results of electrogustometry were not helpful in assessing recovery from taste disturbance, but testing for taste using the filter paper disk method on the posterior portion of the tongue was useful for identifying the onset of recovery.

Adolescent↗
PubMed1981

Active ion transport in dog tongue: a possible role in taste.

An in vitro preparation of the dorsal epithelium of the dog tongue actively transports ions, producing a transepithelial potential difference characteristic of the ions and their concentration. Hypertonic sodium chloride solutions generally cause increased potentials and short-circuit currents and reduced resistances when placed on the mucosal surface. This hypertonic flux is eliminated by ouabain and is not found in ventral lingual epithelia. When either sodium acetate or tetramethylammonium chloride is substituted for sodium chloride in the mucosal medium, the currents are diminished but their sum at a given concentration approximates that for sodium chloride at the same concentration. This result suggests a current composed of inward sodium ion movement and outward chloride ion movement. Actively regulated potentials and currents, whether generated in the taste buds or in supporting cells, may be important in both normal chemotransduction and in taste responses evoked by currents passing through the tongue.

Animals↗
PubMed1996

Development of voltage-dependent currents in taste receptor cells.

Taste buds, the specialized end organs of gustation, comprise a renewing sensory epithelium. Undifferentiated basal cells become taste receptor cells by elongating and extending processes apically toward the taste pore. Mature taste cells are electrically excitable and express voltage-dependent Na+ Ca2+, and K+ currents, whereas basal stem cells exhibit only slowly activating K+ currents. The question we have addressed in the present study is whether contact with the taste pore is required for expression of voltage-dependent inward currents in Necturus taste cells. Mature taste cells were distinguished from developing cells by labeling the apical surface of the cells with fluorescein-isothiocyanate-conjugated wheat germ agglutinin (FITC-WGA), while the tissue was still intact. Elongate cells lacking FITC-WGA staining were interpreted as developing taste cells that had not yet reached the taste pore. Giga-seal whole-cell recording revealed that most developing taste cells lacked inward currents. Although some developing cells expressed inward currents, they were much smaller than those of mature cells, and the activation kinetics of the K+ currents were slower than in mature cells. Electron microscopy confirmed the identity of labeled and unlabeled cells. All FITC-WGA-labeled cells exhibited the ultrastructural characteristics of mature taste receptor cells, whereas most unlabeled taste cells had a characteristic morphology that was markedly different from mature taste receptor cells or basal stem cells. These data suggest that contact with the taste pore is required for the development of inward currents in taste cells.

Animals↗
PubMed1995

[Healing process of taste receptor disturbance].

Patients with taste receptor disturbance were treated with zinc dosage, and their healing process was traced through the filter-paper-disc method and electrogustometry. The number of cases studied was 119,45 with idiopathic taste disturbance, 38 with drug-induced taste disturbance and 36 with zinc-deficient taste disturbance. 1) Three patterns of taste recovery were observed on the tongue surface. Out of a total of 119 cases, 54 cases (45.4%) were found to be improving on the anterior as well as posterior parts of the tongue simultaneously (simultaneous improvement type). Fifty-three cases (44.5%) showed recovery in the posterior part of the tongue (area of the glossopharyngeal nerve) earlier than in other parts of the tongue (posterior improvement type). Only 12 cases (10.1%) showed recovery in the anterior part of the tongue (area of the chorda tympani nerve) earlier than in other parts of the tongue (anterior improvement type), a significantly smaller number of cases compared with the other two types. In particular, very few cases of zinc deficient taste disturbance belonged to the anterior improvement type. Zinc dosage treatment proved to be more rapidly effective for the simultaneous improvement type. 2) With respect to differences in the recovery process of the four primary tastes, a tendency for the sweet and bitter taste qualities to recover earlier than the others was observed in the simultaneous improvement type. However, no phenomenon was observed that could support the existence of the so-called "tongue map", such as the bitter and sour taste recover first among the posterior improvement type or the sweet taste improving first among the anterior improvement type. 3) The results of this study revealed that the treatment of taste receptor disturbances starts with the posterior part of the tongue, which abounds in taste buds. 4) The study also demonstrated that electrogustometry is not suitable for tracing the process of taste receptor disturbance. 5) When tracing the effectiveness of treatment of taste receptor disturbance through the filter paper-disc method, it is sufficient to measure only the posterior part of the tongue (area of the glossopharyngeal nerve) until signs of healing appear.

Adolescent↗
PubMed1977

The effects of feeding a zinc-deficient diet on taste acuity and tongue epithelium in rats.

Taste preferences, fluid intake and histology of tongue epithelium were studied in rats fed a zinc-deficient diet and in pair-fed controls. The results of two-bottle preference tests demonstrated that zinc-deficient rats exhibited significantly increased preferences for 1.5 X 10(-1) M HCL and 1.28 X 10(-6) M quinine sulfate as well as a significant increase in relative fluid volume intake. Histologic examination of the tongue epithelium of the zinc-deficient rats showed a hypercellular prickle cell layer and a marked parakeratosis. The fungiform papillae of the zinc-deficient rats exhibited acanthosis and mild parakeratosis. However, the pore region of the taste buds did not seem to be covered by the parakeratotic epithelium. The results suggest that the impaired taste observed in zinc-deficient rats may not be related to blockage of tastants from the pore region.

Animals↗
PubMed2005

Heat activation of TRPM5 underlies thermal sensitivity of sweet taste.

TRPM5, a cation channel of the TRP superfamily, is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweet, umami and bitter tastes. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and is proposed to generate a depolarizing potential in the taste receptor cells. Factors that modulate TRPM5 activity are therefore expected to influence taste. Here we show that TRPM5 is a highly temperature-sensitive, heat-activated channel: inward TRPM5 currents increase steeply at temperatures between 15 and 35 degrees C. TRPM4, a close homologue of TRPM5, shows similar temperature sensitivity. Heat activation is due to a temperature-dependent shift of the activation curve, in analogy to other thermosensitive TRP channels. Moreover, we show that increasing temperature between 15 and 35 degrees C markedly enhances the gustatory nerve response to sweet compounds in wild-type but not in Trpm5 knockout mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans, including enhanced sweetness perception at high temperatures and 'thermal taste', the phenomenon whereby heating or cooling of the tongue evoke sensations of taste in the absence of tastants.

Animals↗
PubMed1995

Modulation of rat chorda tympani nerve activity by lingual nerve stimulation.

1. A subpopulation of lingual nerve (LN) fibers surround and/or terminate in taste buds in fungiform papillae. One possible function of these fibers is to modulate chorda tympani fiber (CT) or taste responses. To test this hypothesis, the rat LN was stimulated electrically at various voltages (to 20 V), and single- and multiunit CT responses to water-0.1 M NaCl cycles were recorded before, during, and after LN stimulation. 2. When a thermally controlled water-0.1 M NaCl stimulus cycle was applied onto the tongue's surface, the surface temperature remained constant, independent of the stimulation voltage. In the absence of a liquid stimulus, the tongue's surface temperature increased approximately 4 degrees C upon LN stimulation for voltages > or = 5 V. This temperature increase, caused by vasodilation by way of the axon reflex flare mechanism, was taken as evidence that LN stimulation induces peptide release. 3. Comparison of CT activity before LN stimulation with the activity either during or after stimulation revealed statistically significant changes in CT activity. During LN stimulation the CT activity decreased. After LN stimulation, the variability in amount of CT activity increased. 4. In rats treated postnatally with subcutaneous injections of capsaicin to reduce or eliminate polymodal nociceptors, LN stimulation did not produce increases in the tongue's surface temperature or changes in CT activity. 5. Changes in CT activity could be detected seconds after LN stimulation, suggesting that the intragemmal and/or perigemmal LN fibers modulate CT activity. 6. The physiological implications of this study suggest that CT responses to salt can be modulated by endogenous compounds (probably peptides), eating foods that activate LN responses (e.g., foods that are very acidic or contain capsaicin) may modulate taste responses, and peri- and intragemmal fibers should be considered an integral part of the taste receptor system.

Animals↗
PubMed1998

PROP (6-n-propylthiouracil) supertasters and the saltiness of NaCl.

Taste blindness to phenylthiocarbamide (PTC) and its chemical relative 6-n-propylthiouracil (PROP) was discovered in the 1930s. Family studies showed that those who could not taste PTC/PROP (nontasters) carried two recessive alleles. In recent years, we have classified tasters into two groups: medium (PROP is moderately bitter) and supertasters (PROP is intensely bitter). With our classification, approximately 25% of Americans are nontasters, 50%, medium tasters, and 25%, supertasters. Studies showed that supertasters form a cohesive group. Anatomical studies showed that supertasters have the most fungiform papillae. Psychophysical studies showed that supertasters perceive the most intense bitterness and sweetness from a variety of compounds, the most intense burn from oral irritants, and the most intense tactile sensations from viscous solutions. Oral burn and touch are presumably perceived to be the most intense to supertasters because taste buds in fungiform papillae are innervated by the trigeminal nerve (pain, touch) as well as the chorda tympani nerve (taste). The psychophysical scaling method used was magnitude matching with NaCl as the control modality. With this method, subjects rated the intensities of a series of NaCl and PROP solutions. The assumption that the taste of NaCl did not vary with PROP status allowed comparisons of the bitterness of PROP across subjects. Early magnitude matching studies, using sound as the control, had suggested that this assumption was reasonable. However, recent studies challenged that conclusion. Larger samples with more diverse populations, using sound as the control, showed that the taste of NaCl varied with PROP bitterness; supertasters perceived the strongest taste and nontasters, the weakest. Thus our earlier conclusions were conservative because differences between nontasters, medium tasters, and supertasters were concealed by using NaCl as a standard. Using magnitude matching with sound as the standard, or using the Green scale, which employs intensity labels, we found that the differences between PROP groups are larger. Note that the association between PROP status and salt taste is interesting in itself, since variability in salt taste may have important nutritional consequences.

Humans↗