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Chemosensory and somatosensory regeneration after lingual nerve repair in humans.

PURPOSE: The objective of these studies was to measure the impact of Class IV and V lingual nerve injuries on taste sensitivity and taste receptor density of the anterior tongue before and after microneurosurgical repair. MATERIALS AND METHODS: Citric acid detection threshold and suprathreshold magnitude response were measured on the anterior tongue in 12 adult volunteers with unilateral lingual nerve Class IV or V injuries. The right and left sides of the anterior tongue were tested at each session to assess the effect of nerve damage before and 1, 3, 6, and 12 months after repair. Whole-mouth threshold and suprathreshold scales of citric acid taste intensity were measured. The level of sensory impairment was scaled at each test session using a clinical neurosensory test algorithm. Finally, patients completed an 11-item instrument survey that queried the patient's perceived expectations of surgery on sensory, taste, and general health before surgery and the patient's perceived outcome of surgery at each postrepair session. The patient's perceived global satisfaction of surgery was also assessed. RESULTS: All 12 patients failed to detect and scale citric acid and had complete or severe sensory impairment on the injured side of the anterior tongue. One year after repair, 50% of the patients demonstrated a substantial increase in the number of fungiform papillae, pores, and ratio of pores/papilla at the same time as they demonstrated the ability to detect and scale citric acid. After repair, patients perceived the greatest improvements in the categories of eating, chewing, feeling, and taste, and the least in speech. CONCLUSION: Lingual nerve repair may result in significant changes in somatosensory and chemosensory function and taste bud anatomy on the anterior tongue over time.

Adult↗

Anatomical and neurohistological studies on the tongue of the Indian buffalo (Bubalus bubalis).

In the Indian buffalo (Bubalus bubalis), the gross anatomical and neurohistological aspects of the tongue, its tunics and various lingual papillae have been studied. The observations indicate that the widest part of the tongue is also the thickest. The papillae encountered therein include filiform (four sub-types), fungiform and circumvallate papillae. Simple branched tubulo-acinar serous glands are located in the lamina propria of the circumvallate papillae. The mucous glands are limited to the root of the tongue. The nerve endings such as the muscle spindle, ovoid or elliptical and motor end-plates are found to be associated with the skeletal muscle. In the lingual epithelium, only simple free nerve endings are seen. In the taste buds, the intragemmal fibres end in close proximity of the gustatory cells.

Animals↗

Acid and salt responses in mouse taste cells.

Acid and salt responses of taste cells induced by natural stimulation have not been investigated with exception of early studies with conventional microelectrode method, due to the toxicity of high concentration of salt or low pH of acid stimuli applied to isolated taste cells. This indicates that the application of rapid and localized stimulation to the apical membrane of taste cells is necessary for recording of natural responses to salt or acid stimuli using patch clamp technique. Recently we have developed a procedure to accomplish the quasi-natural condition including rapid, localized stimuli to the apical receptive membrane and the maintenance of taste bud polarity. In this review, we present our recent results obtained under quasi-natural condition using patch clamp techniques, comparing with the previously proposed hypothesis. One of our major finding is the fact that the acid-induced responses of taste cells in the mouse fungiform papillae are never suppressed by amiloride but an apical proton-gated conductance and a basolateral Cl(-) conductance possibly contribute to sour transduction. On the other hand, salt-induced responses are suppressed by amiloride, although the salt-induced responses recorded from a single cell involve both amiloride-sensitive and -insensitive components. Furthermore, the amiloride-insensitive component of salt responses possibly consists of multiple subcomponents including an apical sodium-gated nonselective cation conductance and a basolateral Cl(-) conductance. Recent reports also support the hypothesis that both acid and salt responses require specific receptor mechanisms of inorganic cations such as H(+) and Na(+) at the apical receptive membrane.

Acids↗

Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction.

BACKGROUND: Taste receptor cells are responsible for transducing chemical stimuli into electrical signals that lead to the sense of taste. An important second messenger in taste transduction is IP3, which is involved in both bitter and sweet transduction pathways. Several components of the bitter transduction pathway have been identified, including the T2R/TRB taste receptors, phospholipase C beta2, and the G protein subunits alpha-gustducin, beta3, and gamma13. However, the identity of the IP3 receptor subtype in this pathway is not known. In the present study we used immunocytochemistry on rodent taste tissue to identify the IP3 receptors expressed in taste cells and to examine taste bud expression patterns for IP3R3. RESULTS: Antibodies against Type I, II, and III IP3 receptors were tested on sections of rat and mouse circumvallate papillae. Robust cytoplasmic labeling for the Type III IP3 receptor (IP3R3) was found in a large subset of taste cells in both species. In contrast, little or no immunoreactivity was seen with antibodies against the Type I or Type II IP3 receptors. To investigate the potential role of IP3R3 in bitter taste transduction, we used double-label immunocytochemistry to determine whether IP3R3 is expressed in the same subset of cells expressing other bitter signaling components. IP3R3 immunoreactive taste cells were also immunoreactive for PLCbeta2 and gamma13. Alpha-gustducin immunoreactivity was present in a subset of IP3R3, PLCbeta2, and gamma13 positive cells. CONCLUSIONS: IP3R3 is the dominant form of the IP3 receptor expressed in taste cells and our data suggest it plays an important role in bitter taste transduction.

Animals↗

Ultrastructural and histochemical changes in the frog taste organ following denervation.

The fine structure of the taste organ in the Rana catesbeiana was observed by light and electron microscopy. The taste organ consists of three distinct cell types, the taste, supporting and basal cells as well as nerve elements. The present findings suggest that the taste cell might function not only as a chemoreceptor cell, but also as a paracrine cell. The basal cell also may have a dual function as both mechanoreceptor and paracrine cell. Furthermore, taste organs have been examined at intervals from 3 hrs to 120 days after sectioning of the glossopharyngeal nerves. The taste organs were almost intact throughout the experimental period after denervation and even after ceasing to produce impulses from chemical or mechanical stimuli. The dense-cored vesicles of the taste or basal cells, which may possess a paracrine action, still remain in the taste organ even 120 days after denervation. It can be concluded that the morphological integrity of the frog taste organ does not absolutely need the presence of the gustatory fibers in contrast to the nerve-dependent nature of the mammalian taste bud.

Adenosine Triphosphatases↗

Roles of chemical mediators in the taste system.

Recent advances in neural mechanisms of taste are reviewed with special reference to neuroactive substances. In the first section, taste transduction mechanisms of basic tastes are explained in two groups, whether taste stimuli directly activate ion channels in the taste cell membrane or they bind to cell surface receptors coupled to intracellular signaling pathways. In the second section, putative transmitters and modulators from taste cells to afferent nerves are summarized. The candidates include acetylcholine, catecholamines, serotonin, amino acids and peptides. Studies favor serotonin as a possible neuromodulator in the taste bud. In the third section, the role of neuroactive substances in the central gustatory pathways is introduced. Excitatory and inhibitory amino acids (e.g., glutamate and GABA) and peptides (substance P and calcitonin gene-related peptide) are proved to play roles in transmission of taste information in both the brainstem relay and cortical gustatory area. In the fourth section, conditioned taste aversion is introduced as a model to study gustatory learning and memory. Pharmacobehavioral studies to examine the effects of glutamate receptor antagonists and protein kinase C inhibitors on the formation of conditioned taste aversion show that both glutamate and protein kinase C in the amygdala and cortical gustatory area play essential roles in taste aversion learning. Recent molecular and genetic approaches to disclose biological mechanisms of gustatory learning are also introduced. In the last section, behavioral and pharmacological approaches to elucidate palatability, taste pleasure, are described. Dopamine, benzodiazepine derivatives and opioid substances may play some roles in evaluation of palatability and motivation to ingest palatable edibles.

Animals↗

Chemoreceptors expressed in taste, olfactory and male reproductive tissues.

We have identified three genes encoding previously uncharacterized chemoreceptors expressed in rat sensory and reproductive tissues using a reverse transcriptase polymerase chain reaction strategy. Degenerate oligonucleotides designed from conserved sequences in the rat olfactory receptor gene family were used to amplify candidate receptor gene products expressed in taste tissue. Sequence analysis of three distinct clonal isolates revealed that the gene products from taste bud were 30-75% identical to previously identified olfactory receptor genes. The genomic coding sequences predicted protein structures with seven membrane spanning regions that have strong conservation relative to other members of the G-protein-coupled olfactory receptor gene family. Transcripts for each of the three gene products were detected exclusively in taste, olfactory and male reproductive tissue. Sequence analysis of the polymerase chain reaction products confirmed that identical transcripts were expressed in all three tissues. These findings are the first demonstration that identical olfactory receptor-like gene are expressed in three distinct tissues.

Amino Acid Sequence↗

[The sense of taste].

The taste sense is one of the five human senses. It is essential to our survival because it enables the individual the choice of correct food, which, in turn, is crucial for one's existence, maintenance and function. This is a complicated chemical sense, which operates in conjunction with other senses such as vision, smell and touch, and is also associated with the operation of temperature and consistency receptors. There are five basic tastes: bitter, sweet, sour, salty and "fleshy" (umami), each of which has a role in food selection, being responsible for the recognition of certain chemicals, which may be either necessary or dangerous to our body. The taste cell is located in the taste buds, which, in turn, are situated in the tongue, oral cavity and the proximal third of the esophagus. This translates the chemical signal of tastants in food to electrical stimulation that transfers the signal to higher processing centers in the brain, in a process called transduction, which is explained in this review. Disturbances in the taste sense, as well as effects of industrial exposure on this sense are also described. The accumulated knowledge about the taste sense might enable future breakthroughs in the processed food industry.

Brain↗

Demonstration of sensory innervation of rat tongue with anterogradely transported horseradish peroxidase.

Wheat germ agglutinin-horseradish peroxidase injected into the petrosal ganglion in rats was transported to the posterior tongue in the glossopharyngeal nerve. Labelled fibers innervated the ipsilateral foliate papilla only, but both ipsi-and contralateral sides of the single circumvallate papilla. Somatosensory fibers in the posterior tongue also were labelled. Label crossed transcellularly from the afferent fibers into taste bud cells. Use of this method provides more detailed knowledge of sensory innervation of the tongue than previously available.

Animals↗

Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins.

The bitter taste of drugs, food components, and any other substances which get in the mouth as dissolved in an aqueous solution, or in the saliva, can be strongly reduced or fully eliminated, if the bitter component forms an inclusion complex with an appropriate cyclodextrin (CD). The value of the complex association constant (determined by the structure of the bitter 'guest' molecule and the size and eventual substitution of the 'host' CD molecule), the temperature and the host/guest ratio determine the extent of complexation of the guest molecule (percentage of complexation) at the equilibrium. The K(ass) for most drug/CD complexes at 36 degrees C buccal cavity temperature is between 10(2) and 10(4) mol-1. If the unit dose (of a sublingual or chewing tablet, chewing gum) with a bitter drug (molecular weight of about 150, forming a 1:1 complex with betaCD) is approximately 10mg then the betaCD can be taken in a 5- or even 10-fold molar excess. Under such conditions more than 99% of the bitter drug is complexed, and because complexed molecules cannot react with the taste buds in the buccal cavity no bitter taste is perceived. Frequently, preparation of the drug/CD complex is not necessary, because the betaCD is present in a large excess, dissolved very quickly in the saliva and results in a saturated CD solution. Therefore, the complexation of the bitter drug is completed very rapidly. Only dissolved substances have taste and only CD complexable drug molecules can become debittered by CDs. Bitter, astringent components of foods (e.g. soya), beverages (e.g. naringin in citrus fruit juice, or chlorogenic acid and polyphenols in coffee) cigarette smoke (nicotine) also can be complexed and their taste reduced or fully eliminated.

Cyclodextrins↗

Gustatory information of umami substances in three major taste nerves.

The chorda tympani (CT), glossopharyngeal (GL), and greater superficial petrosal (GSP) nerves, the three major branches of cranial nerves innervating taste buds, respond with considerable differences to various taste stimuli. To examine which nerve is responsible for transmitting umami taste in rats, we conducted electrophysiological and behavioral experiments. In the electrophysiological study, responses to umami substances were compared among these three nerves. The CT and GSP were more responsive to mixtures of monosodium L-glutamate (MSG) and 5'-inosine monophosphate (IMP) than the GL. Synergistic effects by the mixture of MSG and IMP were the most prominent in the CT followed by the GSP, whereas it was negligible in the GL. In the behavioral study, rats with a combined transection of the CT and GSP could not acquire conditioned taste aversions to umami substances. These results suggest that umami taste is conveyed more dominantly via the CT and GSP than the GL in the rat.

Animals↗

A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina.

Cyclic nucleotide-gated (CNG) channels are essential proteins that contribute to the intracellular signal transduction of the senses of sight and smell. Recently, we found a novel CNG channel (CNGgust) in rat taste buds, and demonstrated its possible involvement in taste signal transduction. In the present study, we used RT-PCR and immunostaining to prove that this gustatory CNG channel is expressed in the outer segments of rat cone photoreceptor cells. The study strongly suggests that the senses of taste and sight share, at least in part, a common signal transduction pathway.

Animals↗

The effects of aging and how they alter care.

Geriatrics, which is still a young medical specialty, is only just beginning to discover how the elderly react to illness and treatment. One of the discoveries is that the elderly do not always respond or show symptoms in the same way as a younger patient. Some basic understanding of the effects of aging on a person can lead to useful strategies in meeting the elderly's needs. A lack of understanding about changes in the elderly's sense organs probably causes the most frustration in the relationship between the elderly patient and the care provider. The ability to see diminishes in approximately 20 percent of the elderly. Approximately one third experience a hearing loss. The elderly have a decreased number of taste buds, especially those affecting sweet and salty tastes. Their ability to perceive pain, pressure, and temperature may decrease as well. The healthcare professional should be aware of the difference in the geriatric data base from that at other life stages and should look for clues that the elderly patient is suffering from diminished senses.

Aged↗

An age-dependent novel hyperinnervation of circumvallate papillae by tyrosine hydroxylase-containing nerve fibers in NGF-overexpressing transgenic mice.

The density of protein gene product 9.5- and tyrosine hydroxylase-immunoreactive nerve fibers innervating circumvallate papillae of the tongue was substantially increased in transgenic mice that overexpressed nerve growth factor (NGF) when compared with age-matched controls. The fiber density was age-dependent. Only transgenic mice contained NGF-immunoreactive basal cells in the vicinity of taste buds, indicating that target-derived NGF induced novel hyperinnervation of the circumvallate papillae.

Aging↗

Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction.

The activity of taste cells maintained in the intact hamster tongue was monitored in response to acid stimulation by recording action currents from taste receptor cells with an extracellular "macro" patch pipette: a glass pipette was pressed over the taste pore of fungiform papillae and perfused with citric acid, hydrochloric acid, or NaCl. Because this technique restricted stimulus application to the small surface area of the apical membranes of the taste cells, many nonspecific, and potentially detrimental, effects of acid stimulation could be avoided. Acid stimulation reliably elicited fast transient currents (action currents of average amplitude, 9 pA) which were consistently smaller than those elicited by NaCl (29 pA). The frequency of action currents elicited by acid stimuli increased in a dose-dependent manner with decreasing pH from a threshold of about pH 5.0. Acid-elicited responses were independent of K+, Na+, Cl-, or Ca2+ at physiological (salivary) concentrations, and were unaffected by anthracene-9-carboxylic acid, tetraethylammonium bromide, diisothiocyanate-stilbene-2,2'-disulfonic acid, vanadate, or Cd2+. In contrast, amiloride (< or = 30 microM) fully and reversibly suppressed acid-evoked action currents. At submaximal amiloride concentrations, the frequency and amplitude of the action currents were reduced, indicating a reduction of the taste cell apical conductance concomitant with a decrease in cell excitation. Exposure to low pH elicited, in addition to transient currents, an amiloride-sensitive sustained d.c. current. This current is apparently carried by protons instead of Na+ through amiloride-sensitive channels. When citric acid was applied while the taste bud was stimulated by NaCl, the action currents became smaller and the response resembled that produced by acid alone. Because of the strong interdependence of the acid and salt (NaCl) responses when both stimuli are applied simultaneously, and because of the similarity in the concentration dependence of amiloride block, we conclude that amiloride-sensitive Na+ channels on hamster taste receptor cells are permeable to protons and may play a role in acid (sour) taste.

Action Potentials↗

Taste reception.

Recent research on cellular mechanisms of peripheral taste has defined transduction pathways involving membrane receptors, G proteins, second messengers, and ion channels. Receptors for organic tastants received much attention, because they provide the specificity of a response. Their future cloning will constitute a major advance. Taste transduction typically utilizes two or more pathways in parallel. For instance, sweet-sensitive taste cells of the rat appear to respond to sucrose with activation of adenylyl cyclase, followed by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent membrane events and Ca2+ uptake. The same cells respond differently to some artificial sweeteners, i.e., with activation of phospholipase C (PLC) followed by inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release from intracellular stores. Some bitter tastants block K+ channels or initiate the cascade receptor G1 protein, PLC, IP3, and Ca2+ release or the cascade receptor alpha-gustducin, phosphodiesterase (PDE), cAMP decrease, and opening of cAMP-blocked channels. Membrane-permeant bitter tastants may elicit a cellular response by interacting with G protein, PLC, or PDE of the above cascades. Salt taste is initiated by current flowing into the taste cell through cation channels located in the apical membrane, even though basolateral channels may also contribute (following salt diffusion through paracellular pathways). In rodents, the Na+-specific component of salt taste is typically mediated by apical amiloride-sensitive Na+ channels, but less specific and not amiloride-sensitive taste components exist in addition. Sour taste may in part be mediated by amiloride-sensitive Na+ channels conducting protons, but other mechanisms certainly contribute. Thus the transduction of taste cells generally comprises parallel pathways. Furthermore, the transduction pathways vary with the location of taste buds on the tongue and, of course, across species of animals. To identify these pathways, to understand how they are controlled and why they evolved to this complexity are major goals of present research.

Animals↗

The blood circulation of the tongue.

This article describes the gross anatomy of the vessels which supply the mammalian tongue. It shows that there is a rich vascular supply. Available data indicate that the lingual papillae are supplied with a true capillary circulation, which is more abundant in the papillae containing taste buds. The vessels of the tongue are innervated by adrenergic sympathetic vasconstrictor fibers and it is also very likely that a cholinergic parasympathetic vasodilator influence exists.

Animals↗

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

Action Potentials↗