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Taste receptor cells arise from local epithelium, not neurogenic ectoderm.

Except for taste bud cells, all sensory receptor cells and neurons have been shown to originate from neurogenic ectoderm (i.e., neural tube, neural crest, or ectodermal placodes). Descriptive studies on taste buds indicate that they, however, may arise from local epithelium. To determine whether taste receptor cells originate from neurogenic ectoderm or from local epithelium, the tongues of X chromosome-inactivation mosaic mice were examined. Results of this analysis show that taste bud cells and their surrounding epithelium always match in terms of the mosaic marker. This suggests that taste cells and epithelial cells arise from a common progenitor and that taste receptor cells originate from local tissue elements. Since taste buds are widespread in the oropharynx, they lie in epithelium derived from both ectoderm and endoderm. Therefore, taste receptor cells can be induced in tissue from two different germ layers. Thus in terms of tissues of origin, taste receptor cells are unlike other cells with neuronal characteristics.

Animals↗

Taste dysfunction in patients receiving radiotherapy.

BACKGROUND: Taste loss is a major cause of morbidity in patients undergoing head and neck irradiation. METHODS: In a prospective study, 51 patients undergoing radical head and neck irradiation at the Tokyo University Hospital were assessed for taste loss. Taste ability was measured by the taste threshold for the four basic tastes (sweet, sour, salt, and bitter qualities) plus another taste of "umami" quality using a filter-paper-disc method in patients before, during, and after radiotherapy (RT). RESULTS: All tastes declined on the fifth week after the start of RT and improved on the 11th week. Anatomic pathologic analyses in rats revealed that taste buds diminished completely on the sixth day after irradiation of 15 Gy in a single fraction, and the appearance of taste buds returned almost to the preirradiation state on the 28th day. CONCLUSIONS: The main cause of taste disorder resulting from RT was believed to be a disappearance of taste buds and not damage to the taste nerves.

Adult↗

The sense of taste: neurobiology, aging, and medication effects.

The sense of taste is an oral chemical sense in mammals that is involved in the choice of foods. Initial transduction of taste stimuli occurs in taste buds, which are distributed in four discrete fields in the oral cavity. Medications can affect the taste buds and ion channels in taste-bud cell membranes involved in stimulus transduction. The sense of taste gradually declines with aging, with bitter taste most affected. Neural circuits that mediate taste in primates include cranial nerves VII, IX, and X, the solitary nucleus in the brain stem, the ventroposteromedial nucleus of the thalamus, and the insular-opercular cortex. The central taste pathways process taste information about sweet, salty, sour, and bitter stimuli serially and in parallel. Medications associated with "metallic" dysgeusia and taste losses affect the taste system via unknown mechanisms.

Aging↗

Umami taste responses are mediated by alpha-transducin and alpha-gustducin.

The sense of taste comprises at least five distinct qualities: sweet, bitter, sour, salty, and umami, the taste of glutamate. For bitter, sweet, and umami compounds, taste signaling is initiated by binding of tastants to G-protein-coupled receptors in specialized epithelial cells located in the taste buds, leading to the activation of signal transduction cascades. Alpha-gustducin, a taste cell-expressed G-protein alpha subunit closely related to the alpha-transducins, is a key mediator of sweet and bitter tastes. Alpha-gustducin knock-out (KO) mice have greatly diminished, but not entirely abolished, responses to many bitter and sweet compounds. We set out to determine whether alpha-gustducin also mediates umami taste and whether rod alpha-transducin (alpha(t-rod)), which is also expressed in taste receptor cells, plays a role in any of the taste responses that remain in alpha-gustducin KO mice. Behavioral tests and taste nerve recordings of single and double KO mice lacking alpha-gustducin and/or alpha(t-rod) confirmed the involvement of alpha-gustducin in bitter (quinine and denatonium) and sweet (sucrose and SC45647) taste and demonstrated the involvement of alpha-gustducin in umami [monosodium glutamate (MSG), monopotassium glutamate (MPG), and inosine monophosphate (IMP)] taste as well. We found that alpha(t-rod) played no role in taste responses to the salty, bitter, and sweet compounds tested or to IMP but was involved in the umami taste of MSG and MPG. Umami detection involving alpha-gustducin and alpha(t-rod) occurs in anteriorly placed taste buds, however taste cells at the back of the tongue respond to umami compounds independently of these two G-protein subunits.

Animals↗

Taste neurons have multiple inductive roles in mammalian gustatory development.

The embryonic loss of brain-derived neurotropic factor (BDNF)-dependent taste axons in bdnf null mutant mice secondary impairs the development of gustatory epithelia and taste buds. In normal mice gustatory development continues for at least two weeks postnatally as axons promote taste bud formation. We conclude that taste axons in the fungiform, foliate, vallate and nasopalate papillae: i) promote papilla development, and ii) establish competent gustatory cells and iii) mature taste buds. Hence, gustatory innervation contributes critically to at least three of the multiple inductive interactions controlling the development of mammalian gustatory structures.

Animals↗

Responses of single facial taste fibers in the sea catfish, Arius felis, to amino acids.

1. Taste buds in catfish are found not only within the oropharyngeal cavity, as in mammals, but are also located along the external body surface of the animal from the barbels and lips to the caudal fin. Because these taste buds are innervated by the facial (cranial VII) nerve, the extraoral taste system of catfish is analogous to the mammalian taste system of the anterior two-thirds of the tongue, which contains taste buds innervated by the chorda tympani nerve, and of the soft palate and nasoincisor ducts, which contain taste buds innervated by the greater superficial petrosal nerve. 2. The majority of information concerning the specificity of individual taste fibers in vertebrates has been obtained primarily in mammals to stimuli representing the four basic human taste qualities (i.e., salty, sweet, sour, and bitter). In the present report, we examine the evidence for gustatory fiber types within the stimulus class of amino acids, compounds known to be especially relevant gustatory stimuli for catfish and other teleosts. 3. Action potentials were recorded from 60 individual facial taste neurons obtained from 28 sea catfish (Arius felis). Stimuli were 10(-4) M concentrations of L-alanine, D-alanine, glycine, L-proline, L-histidine, and L-arginine, compounds selected from an original stimulus list of 28 amino acids. Responses were quantified as the number of action potentials evoked at various time intervals from the first 0.5 s up to 10 s of response time. 4. The spontaneous activity of 42 fully characterized neurons was 0.8 +/- 2.1 SD spikes/3 s. The average rate of spike discharge increased 50-fold during stimulation with the most effective amino acid (42 +/- 31 spikes/3 s, mean +/- SD). The majority of the sampled neurons were not narrowly tuned to the amino acid stimulants tested (mean breadth of responsiveness, H = 0.60; range 0-0.95). 5. Hierarchical cluster analysis of the fully characterized neurons identified two large and two small groups of cells. The largest group (n = 22) of neurons was stimulated most by L-alanine and glycine; the other large group (n = 17) was stimulated most by D-alanine. For this latter group, the response to glycine was relatively low, whereas the responses to L-alanine varied from 0 to nearly 100% of the D-alanine response.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Ion transport across lingual epithelium is modulated by chorda tympani nerve fibers.

Each chorda tympani (CT) nerve innervates taste cells in fungiform papillae on one side of the anterior two-thirds of mammalian tongues. In this study, three effects of unilateral CT transection were investigated: (1) the persistence of taste cells on the ipsilateral and contralateral sides; (2) the ability of the CT to modulate ion transport across the ipsilateral and contralateral sides of canine lingual lingual epithelia; and (3) the effect on contralateral CT responses. Unilateral transection of dog CT caused the mean number of taste buds/fungiform papilla on the ipsilateral side to decrease from five to zero by 29-30 days after surgery. Taste buds reappeared after 44 days but in reduced numbers (two taste buds/papilla). This reappearance of taste buds after 44 days is consistent with the time predicted for the CT to regenerate and reach the anterior portion of the tongue. The number of taste buds/papilla remained unchanged on the contralateral side. Measurements of the short-circuit current (Isc) across both ipsilateral and contralateral sections of isolated canine lingual epithelia were performed at various times after unilateral CT transection. Both sides responded similarly. The Isc began to decline after 3 days, reached a minimum after approximately 18 days (approximately 40% of control Isc) and increased to control values after approximately 40 days. This includes experiments performed 30 days after surgery, when no taste buds were present on the ipsilateral side and the Isc was 80% of control values. For all times after CT transection, amiloride, an epithelial Na+ channel blocker, inhibited Isc. Thus, epithelial cells in dog tongue have amiloride-inhibitable pathways. These results show that proteins involved in active Na+ transport across lingual epithelial can be modulated by CT nerve fibers.

Animals↗

Morphological characteristics of the tongue and its papillae in the donkey (Equus asinus): a light and scanning electron microscopical study.

The morphology of the donkey tongue and its papillae were investigated by macroscopy and by light and scanning electron microscopy in ten adult animals (six males and four females). The spatula-shaped tongues measured about 28 cm in length, 4.5 cm in breadth and 3.5 cm in thickness. Samples from different areas of four tongues were grossly examined and pieces were processed for light and scanning electron microscopy. Filiform papillae were distributed mainly on the dorsum of the tongue, being thin and relatively short at the apex, conical and scaly in the main part (triangular zone) of the body, and thin and longer at the caudal part of the body. Few of them were found on the lateral surfaces. Fungiform papillae appeared scattered mainly on the lateral surfaces. They were mostly rounded (about 1.0 mm in diameter), but lobulated forms were also observed. Filiform and fungiform papillae were both completely devoid of taste buds, indicating a more mechanical function. The vallate papillae were 2-3 in number, located at the most caudal part of the body. They were three to four times as large as the fungiform papillae (about 5.6 mm in diameter) each with a wide circular groove around the central bulbous projection. Secondary grooves originating from the primary one were also demonstrated. The vallate papillae contained many taste buds with taste pores opening deeply into the papillary groove. Fine filiform papillae were demonstrated on the bulb-like part of the vallate papillae. The donkey tongue had sinister and dexter well-developed sets of foliate papillae close to the basis of the palatoglossal arch. They were arranged in the form of numerous leaves separated by deep, variably wide grooves and contained a very large number of taste buds. It is believed that the existence of well developed foliate papillae in donkey may substitute the comparatively few vallate papillae in this species.

Animals↗

Effects of chorda-lingual nerve injury and repair on human taste.

Citric acid detection threshold and magnitude response were measured on the anterior tongue in 10 patients with unilateral chorda-lingual nerve transections before and after repair. Fungiform taste buds were analysed by videomicroscopy. Preliminary data suggests that humans can regenerate fungiform taste buds and recover some taste sensitivity after repair.

Adult↗

Taste responses of cortical neurons.

Branches of the facial, glossopharyngeal and vagus nerves which synapse with the receptor cells in the taste buds convey taste messages to the rostral part of the nucleus of the solitary tract. The second relay nucleus for ascending taste input is the parabrachial nucleus of the pons. The third relay nucleus is the medial parvocellular component of the ventrobasal complex of the thalamus. This thalamic nucleus projects to the cortical taste area. Another ascending projection site of the parabrachial nucleus is to the lateral hypothalamus, amygdala and bed nucleus of the stria terminalis. In monkeys, neurons from the gustatory area of the solitary nucleus directly reach the thalamic taste area, bypassing the parabrachial nucleus. Taste-elicited reflex activities are based on a hedonic (acceptable or rejective) aspect of taste, and are basically determined in the brain stem without activation of cortical neurons. The cerebral cortical taste area is located dorsal to the rhinal sulcus in or near the insular cortex in different species of animals. Besides this taste area, taste inputs also project to the tongue tactile area of the SI in monkeys, cats and rats. Taste-responsive neurons in SI area are also responsive to light tactile stimulation of the tongue. Human clinical case reports suggest that discrimination or recognition of taste quality are processed in the cortical taste area. In animal experiments, it is difficult to determine the functional significance of this area. However, recent behavioral studies using the conditioned taste aversion technique in rats suggest that the cortical taste area plays an important role in cognitive (learning, memorial, associative and discriminative) processes of taste sensation. Summated cortical evoked potentials have been recorded in human and rats to electrical and taste stimulations applied to the tongue surface. Recording of gustatory primary evoked potentials is unsuccessful in human subjects. The responses to taste stimulation are composed of an early component, which is induced by mechanical stimulation of a test solution poured on the tongue surface and a slow component, which is assumed to be the gustatory response. Essentially similar results are obtained for cortical summated responses to taste stimuli in rats. Besides these averaged evoked potentials, arousal changes of EEG occur in response to taste stimulation. There is a possibility that the arousal response can be used an objective indicator for intensity and hedonics of perceived taste sensation.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Tastes associated with parenteral chemotherapy for breast cancer.

We employed a structured interview to retrospectively study tastes and vomiting associated with the parenteral components of cyclophosphamide, methotrexate, and 5-FU in 45 patients with stage II-IV breast cancer. Sixteen patients (36%) reported tastes which generally occurred in each cycle within 30 minutes of parenteral drug administration, lasted less than or equal to 1 hour, and were bitter. Five patients recalled that tastes seemed to produce vomiting. Tasting was significantly associated with postchemotherapy (P less than 0.01) but not anticipatory vomiting. Employing logistic regression techniques, tasting did not significantly improve prediction of anticipatory vomiting by postchemotherapy vomiting. Tastes may be produced by the action of plasma or salivary cyclophosphamide, methotrexate, and 5-FU on taste buds. While tastes might cause some vomiting, they are not necessary for it. Because this was a retrospective study with a small sample, these findings require confirmation.

Antineoplastic Combined Chemotherapy Protocols↗

Sweet taste transduction in hamster: role of protein kinases.

Two different second-messenger pathways have been implicated in sweet taste transduction: sugars produce cyclic AMP (cAMP), whereas synthetic sweeteners stimulate production of inositol 1,4, 5-tris-phosphate (IP(3)) and diacylglycerol (DAG). Both sugars and sweeteners depolarize taste cells by blocking the same resting K(+) conductance, but the intermediate steps in the transduction pathways have not been examined. In this study, the loose-patch recording technique was used to examine the role of protein kinases and other downstream regulatory proteins in the two sweet transduction pathways. Bursts of action currents were elicited from approximately 35% of fungiform taste buds in response to sucrose (200 mM) or NC-00274-01 (NC-01, 200 microM), a synthetic sweetener. To determine whether protein kinase C (PKC) plays a role in sweet transduction, taste buds were stimulated with the PKC activator PDBu (10 microM). In all sweet-responsive taste buds tested (n = 11), PDBu elicited burst of action currents. In contrast, PDBu elicited responses in only 4 of 19 sweet-unresponsive taste buds. Inhibition of PKC by bisindolylmaleimide I (0.15 microM) resulted in inhibition of the NC-01 response by approximately 75%, whereas the response to sucrose either increased or remained unchanged. These data suggest that activation of PKC is required for the transduction of synthetic sweeteners. To determine whether protein kinase A (PKA) is required for the transduction of sugars, sweet responses were examined in the presence of the membrane-permeant PKA inhibitor H-89 (10 and 19 microM). Surprisingly, H-89 did not decrease responses to either sucrose or NC-01. Instead, responses to both compounds were increased in the presence of the inhibitor. These data suggest that PKA is not required for the transduction of sugars, but may play a modulatory role in both pathways, such as adaptation of the response. We also examined whether Ca(2+)-calmodulin dependent cAMP phosphodiesterase (CaM-PDE) plays a role in sweet taste transduction, by examining responses to sucrose and synthetic sweeteners in the presence of the CaM-PDE inhibitor W-7 (100 microM). Inhibition resulted in an increase in the response to sucrose, whereas the response to NC-01 remained unchanged. These data suggest that the pathways for sugars and sweeteners are negatively coupled; the Ca(2+) that is released from intracellular stores during stimulation with synthetic sweeteners may inhibit the response to sucrose by activation of CaM-PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Sublingual structures in primates. Part 1: Prosimiae, Platyrrhini and Cercopithecinae].

1. The sublingual structures of primates have been studied light-microscopically. There are 3 different sublingual structures in the species studied. The plica sublingualis occurs in all primates. The sublingual organ is a topographically modified plica sublingualis which occurs exclusively in Callicebus. A sublingua is present only in the prosimians. 2. The plica sublingualis contains the excretory ducts of the submandibular and sublingual salivary glands. The sublingua is ventrally adherent to the body of the tongue and is, with a few exceptions in Tupaia, characterized by a skeleton of cartilage tissue. A sublingua never exhibits excretory ducts or salivary glands. 3. In some Platyrrhini (Ateles, Aotus, Lagothrix, Alouatta, Callicebus), there are taste buds in the epithelium of the plica sublingualis. They are especially concentrated near the orifices of the salivary glands. 4. The fresh saliva of the submandibular and sublingual gland can be tested by the taste buds on the plica sublingualis, because there is a topographical coincidence. 5. There is a complete absence of taste buds at the plica sublingualis of the prosimians and the Cercopithecinae. 6. There are no taste buds in the epithelium of the sublingua. In the Lorisiformes and in the Lemuriformes the sublingua is a cleaning device of the anterior dentition, most probably in connection with a tactile sensibility. In the Tupaiformes and in the Tarsiiformes the sublingua is less developed. 7. There is no anatomical connection between the skeleton of cartilage tissue in the sublingua and the lytta, or the skeleton of the hyoideum. 8. In some Cercopithecinae (Macaca, Papio) a glandula apicis linguae is present.

Animals↗

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↗

Chemoreceptive and mechanoreceptive paraneurons in the tongue.

Chemoreceptive and mechanoreceptive paraneurons in the tongue include gustatory cells and basal cells of the taste buds, Merkel cells in the lingual epithelium and Merkel or Grandry corpuscles in avian subepithelial connective tissue. Neuron-specific enolase immunoreactivity is recognized in the basal cells, a type of Merkel cells, in the taste buds of teleost fishes and amphibia, certain taste bud cells of mammals and the Merkel cells in birds. The present study also concerns itself with the ultrastructural features of the gustatory cells of the rabbit taste buds, and the Merkel cells of the finch tongue. The functional significance of the dense-cored granules in the gustatory cell is still enigmatic. On the other hand, the dense-cored granules in the Merkel cells may have dual functions storing both neurotransmitters and local hormones. Shortly after giving a mechanical stimulus to the finch tongue, we could demonstrate massive exocytotic changes of the Merkel cell granules.

Amphibians↗

The gustatory sense in foetal sheep during the last third of gestation.

1. Histological studies revealed that presumptive taste buds are present in the foetal sheep tongue at 50 days. By 100 days the taste buds appear morphologically mature.2. To determine if foetal taste buds are functional, electrophysiological recordings were made of activity in the chorda tympani nerve of sheep foetuses. Single and multi-fibre preparations were studied in foetuses aged 100 days to term.3. Responses were recorded to lingual stimulation with salts, acids, glycerol, glycine, sodium saccharin, quinine HCl and amniotic fluid. Responses of the foetal chorda tympani to lingual stimulation with a series of monochloride salts and with increasing concentrations of one salt were similar to responses recorded in lambs and adults.4. The peripheral gustatory system of the foetal sheep is functional for at least the last third of gestation. Foetal taste experiences may influence the formation of adult taste preferences or may aid the foetus in monitoring its environment.

Acetates↗

Taste receptor cells express voltage-dependent potassium channels in a cell age-specific manner.

Two voltage-dependent potassium channels, KCNQ1 and KCNH2, are expressed in the taste buds and were identified as strong candidates involved in the repolarization of taste receptor cells expressing phospholipase C-beta2 and TRPM5 (beta2/M5-TRCs). In cell type-specific expression, KCNQ1 was expressed in most taste bud cells, including beta2/M5-TRCs, whereas KCNH2 was expressed in a subset of beta2/M5-TRCs with no correlation with their taste modality, such as sweet or bitter taste reception. Expression of KCNH2 was restricted to young beta2/M5-TRCs. These results suggest that taste bud cells other than beta2/M5-TRCs are depolarized by some stimuli and also that beta2/M5-TRCs have cell age-dependent molecular mechanisms of repolarization.

Action Potentials↗

Lingual BDNF and NT-3 mRNA expression patterns and their relation to innervation in the human tongue: similarities and differences compared with rodents.

Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNAs are expressed in developing and adult rodent tongue and are important for the proper development of lingual gustatory and somatosensory innervation in rodents. Here, we wished to determine whether the findings in rodents apply to humans. By using in situ hybridization histochemistry, distinct, specific, and in some instances overlapping patterns of BDNF and NT-3 mRNA expression were found in the developing and adult human tongue, gustatory papillae, and taste buds. BDNF mRNA was expressed in the superior surface epithelium of the developing fungiform papillae (i.e., developing taste buds), in the epithelium covering the circumvallate papillae, and in the subepithelial mesenchyme. Interestingly, BDNF mRNA was expressed in the lingual epithelium before nerve fibers reached the epithelium, indicating a prespecialization of the gustatory epithelium before the arrival of nerves. In the adult fungiform papillae, BDNF mRNA labeling was found in taste buds and in restricted areas in the non-gustatory lingual epithelium. NT-3 mRNA was found in the developing lingual epithelium and gustatory papillae. NT-3 mRNA labeling was observed in the adult fungiform taste buds, overlapping with BDNF mRNA labeling, in contrast to what was seen in rodents. NT-3 mRNA was additionally found in restricted areas in filiform papillae. Protein gene product 9.5 (PGP) antibodies were used to investigate a possible correlation between lingual innervation and sites of neurotrophin gene activity. Adult human tongue innervation differed from that of rodents, possibly in part due to a different neurotrophin expression pattern in the human tongue. Based on these findings, we suggest that BDNF and NT-3 are important for the initiation and maintenance of the gustatory and somatosensory innervation also in humans. The broader and somewhat overlapping expression patterns of BDNF and NT-3 mRNAs, compared with rodents, suggest additional and possibly somewhat overlapping roles for BDNF and NT-3 in the human tongue and also indicate differences between species. It is important that interspecies differences be taken into consideration.

Adult↗