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The combination effect of L-arginine and NaCl on bitterness suppression of amino acid solutions.

The purpose of the present study was to quantify the degree of suppression of the bitterness of two amino acids (L-isoleucine (L-Ile), and L-phenylalanine (L-Phe)) which could be achieved by the addition of various test chemicals, and to examine the mechanism of this bitterness suppression. The test chemicals used were two sweeteners (sucrose, aspartame), NaCl, various acidic (L-aspartic acid, L-glutamic acid), or basic (L-histidine, L-lysine and L-arginine) amino acids, tannic acid and phosphatidic acid. The combination of L-arginine (L-Arg) and NaCl together was the most effective in reducing the bitterness of 100 mM L-Ile and L-Phe solutions in human gustatory sensation tests. Even in bitterness of 0.1 mM quinine solution, L-Arg was also successful in reducing the bitterness. This bitterness-suppression effect was specific to L-Arg and not to the other basic amino acids. No comparable taste-masking effect was observed for the acidic amino acids. The artificial taste sensor failed to predict completely the bitterness-suppressing effect of L-Arg. It seems likely that the bitterness-suppressing effect of L-Arg is mediated not only by binding at the receptor site, but also elsewhere in the process of bitterness perception, such as a direct effect on the sodium channel. It is conjectured that the guanidinium group of L-Arg may interact with sodium channels in taste bud membranes.

Arginine↗

Behavioral displays to gustatory stimuli in newborn rat pups.

These experiments examine behavioral responses to taste stimuli in newborn rat pups during the first 4 postnatal days. Motor displays in the face and head regions of 90 neonate rats were recorded during 60-sec observation periods in a double-blind setting. Stimuli, presented as single droplets to the lips, included 2 concentrations each of sucrose, sodium saccharin, citric acid, quinine, and distilled water. Results from 5 different judges making "blind" and independent observations on different animals were compared for concordance. It was agreed that certain features were consistently associated with one stimulus more than another. Licking and rhythmic mouth movements were found to be the most salient features elicited by sweet stimuli, while head movements and gaping most accurately identified quinine. The sour reaction often contained components characterizing both sweet and bitter. Salient features differed not only by their association with certain stimuli, but by their repetitive frequencies as well as by their likelihood to initiate a behavioral sequence. Intensity and hedonic values assigned to taste-induced behaviors were usually different from water and accurately related to stimulus type. Results suggest that the gustatory system becomes functionally mature during the first postnatal days, and that this functionality occurs before the structural development of all taste buds is complete.

Animals↗

The anion paradox in sodium taste reception: resolution by voltage-clamp studies.

Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

Animals↗

Effects of drugs on olfaction and taste.

The fact that so many varied medications reportedly affect taste and smell is a testament to the complexity of the gustatory and olfactory systems. The reception, transduction, propagation, and perception of a chemical tastant or odorant requires the effective operation of numerous mechanisms--all of which may be susceptible in one way or another to a prescribed medication. Just as a diuretic may block the apical ion channels on a taste bud, or an antifungal can inhibit cytochrome p450-dependent enzymes at the level of the receptors, a chemotherapeutic agent can destroy mitosis in a replicating receptor cell and a steroid can lead to candidal overgrowth on the tongue surface. Medications not only have a perceivable taste themselves at times, but they can alter the mechanisms responsible for the ultimate perception of tastes and smells--either by direct or secondary means. It should be emphasized, as noted earlier in this article, that while many medications are to blame for the impairment or distortion of the gustatory or olfactory systems, it is not uncommon that the underlying medical problem for which they are prescribed is actually the culprit. Examples include epilepsy, migraines, hypothyroidism, schizophrenia, infections, and cancer. In fact, simple partial seizures emanating from regions of the brain such as the amygdala, hippocampus, parietal operculum, and rolandic operculum can lead to the chemosensory sensations that are most commonly considered unpleasant, such as "rotten apples," "cigarette," "peculiar," or "vomitus". While removing or changing an offending medication can reverse the effects on smell or taste perception, it is important to remember that lasting impairment may occur. This is vital for a physician to recognize prior to prescribing a medication. It is also necessary to report this to patients who may be devastated by chemosensory alterations after starting a new medication (eg, pastry chef, perfumist, wine specialist, plumber). Among the "risks" in a risks/benefits discussion with a patient regarding the use of a new medication, alterations in olfaction and taste appear to play an increasingly recognized role.

Drug-Related Side Effects and Adverse Reactions↗

A history of sweeteners--natural and synthetic.

Sweetness for the prehistoric man was the taste sensation obtained from sweet berries and honey. Man's quest for other sweet things led to sucose, starch-derived sugars, and synthetic sweeteners. An unusual source of sweet taste is a West African berry known as miracle fruit (Synsepalum dulcificum). This fruit possesses a taste-modifying substance that causes sour foods--e.g., lemons, limes, or grapefruit--to taste sweet. The active principle was found to be a glycoprotein. Until this time, only small molecules were considered sweet-evoking substances, but now macromolecules are considered capable of participating in taste perception. The intense sweetener of the fruit of Dioscoreophyllum cumminsii, called the serendipity berry, was revealed to be a protein. The intensely sweet principle of Thaumatococcus daniellii, called katemfe, was reported in 1972 to contain two proteins having intense sweetness. Since intensely sweet protein sweeteners act directly on taste buds as a probe, a peptide linkage analogous to the aspartic acid sweeteners may be partly responsible for their sweetness.

History of Medicine↗

Structural relationships of sugars to taste.

Chemical modification of sugars and their simple analogues indicates that these types of compound are almost always sweet, bitter, or bitter/sweet; hence, the two basic tastes may be intimately associated features of the same molecule. Stepwise modification at each chiral center around the sugar ring allows the sapid functions in these molecules to be mapped and leads to the inescapable conclusion that sugar molecules may be "polarized" on taste bud receptors, so that one end of the molecule elicits sweetness and the other bitterness. However, more extensive chemical modification evidently causes the molecule to realign itself in entirely different ways on the receptor. In most oligosaccharides only one sugar residue is likely to bind to the taste receptor, and this is probably a nonreducing end group, because the anomeric center of glucopyranose types of structure does not appear to affect sweetness. Sweetness depresses bitterness and bitterness depresses sweetness. Hence, it is not possible to make structural comparisons between analogues without correcting for these effects. However, some semiquantitative studies have established the value of current hydrogen bond theories of sweetness and the ideal oxygen-oxygen interorbital spacings for sweetness criteria in sugar molecules.

Acetates↗

Responses of the hamster chorda tympani nerve to binary component taste stimuli: evidence for peripheral gustatory mixture interactions.

Studies of taste mixtures suggest that stimuli which elicit different perceptual taste qualities physiologically interact in the gustatory system and thus, are not independently processed. The present study addressed the role of the peripheral gustatory system in these physiological interactions by measuring the effects of three heterogeneous taste mixtures on responses of the chorda tympani (CT) nerve in the hamster (Mesocricetus auratus). Binary taste stimuli were presented to the anterior tongue and multi-fiber neural responses were recorded from the whole CT. Stimuli consisted of a concentration series of quinine.HCl (QHCl: 1-30 mM), sodium chloride (NaCl: 10-250 mM), sucrose (50-500 mM) and binary combinations of the three different chemicals. Each mixture produced a unique pattern of results on CT response magnitudes measured 10 s into the response. Sucrose responses were inhibited by quinine in QHCl-sucrose mixtures. Neural activity did not increase when quinine was added to 50-250 mM NaCl in QHCl-NaCl mixtures. However, the neural activity elicited by sucrose-NaCl mixtures was greater than the activity elicited by either component stimulus presented alone. The results demonstrate that gustatory mixture interactions are initiated at the level of the taste bud or peripheral nerve. Mechanisms for these interactions are unknown. The results are consistent with one component stimulus modifying the interaction of the other component stimulus with its respective transduction mechanism. Alternatively, peripheral inhibitory mechanisms may come into play when appetitive and aversive stimuli are simultaneously presented to the taste receptors.

Analysis of Variance↗

Role of submandibular and sublingual saliva in maintenance of taste sensitivity recorded in the chorda tympani of rats.

1. To evaluate the role of saliva in the maintenance of taste sensitivity, the activities in the rat chorda tympani innervating taste buds in the anterior part of the tongue were analysed. The effects of chronic extirpation of the submandibular and sublingual salivary glands were tested and compared with results after chronic oral administration of artificial saliva. 2. Removal of the salivary glands sharply decreased chorda tympani responses to four different taste stimuli by 7 days post-desalivation, while a stable response to cold water was observed by at least 28 days. 3. This selective decrease in taste responses was considerably recovered by 7-day-oral injection of artificial saliva (containing NaHCO3, KCl and/or mucin) or distilled water. However, the injection of the salt-containing artificial saliva induced significantly larger sucrose and smaller NaCl, HCl and quinine responses than did the injection of distilled water. 4. In our salivary manipulations, an alteration in the number of the functional sweet receptors was suggested by the cross-adaptation technique using NaHCO3, whereas sensitivity to the epithelial sodium transport blocker, amiloride, was stable in the NaCl response. 5. Salivary water and electrolytes which may participate in forming the external environment of the taste receptor cells modulated taste sensitivity in the chorda tympani.

Adaptation, Physiological↗

A Golgi analysis of the gustatory zone of the nucleus of the solitary tract in the adult hamster.

The somal shapes, dendritic features, and orientations of the neurons within the gustatory zone of the nucleus of the solitary tract were studied with the rapid Golgi method in the adult hamster. These Golgi studies complement previous quantitative morphometric analyses of the distributions of large and small neurons within the gustatory zone. Class 1 neurons are usually fusiform and possess long, relatively unbranched dendrites that often extend beyond the cytoarchitectonic boundaries of the gustatory zone. Class II neurons are multipolar and possess more dendrites that are significantly shorter than those of class I neurons. Both classes of neurons are spine poor. Computer-generated three-dimensional rotational analyses demonstrate that the dendritic arborizations of neurons of the gustatory zone are oriented preferentially in the horizontal plane. Dendrites extend in parallel or perpendicular to the solitary tract, the source of peripheral gustatory inputs, and appear to be positioned spatially to maximize synaptic interactions with these peripheral fibers. These Golgi studies also suggest that individual gustatory neurons may be influenced by incoming gustatory fibers that innervate separate populations of taste buds, a finding that is not predictable from the topographical organization of the gustatory zone.

Animals↗

Plasma retinol transport system and taste acuity in patients with obstructive jaundice.

A study was conducted to elucidate the correlation between the plasma retinol transport system and taste acuity in patients with obstructive jaundice (OJ). Plasma levels of retinol, retinol-binding protein (RBP), transthyretin (TTR) and holo-RBP (retinol-RBP complex unbound to TTR), as well as the threshold of taste acuity, were determined in 8 cases with OJ (6 cases with common bile duct cancer and 2 cases with pancreas head cancer) and in 20 apparently healthy volunteers. These parameters were also measured serially in patients with OJ before and after percutaneous transhepatic biliary drainage (PTBD). Plasma levels of retinol, RBP and TTR were significantly decreased in every patients with OJ as compared with healthy controls, whereas changes in holo-RBP levels were not consistent. Taste acuity was found to be reduced in patients with decreased holo-RBP levels, while the acuity was preserved well in patients whose holo-RBP levels remained normal. Impaired taste acuity was rapidly improved in every patients after treatment with PTBD, significantly correlating with the recovery of plasma RBP and holo-RBP levels, and with the reduction of plasma total bilirubin levels. These results suggest that taste acuity is affected by the plasma retinol transport system, including serum levels of holo-RBP, from which retinol is delivered, presumably through a receptor-mediated manner, to the taste buds.

Adult↗

Taste function in Sjögren's syndrome patients with special reference to clinical tests.

OBJECTIVE: We analyzed the correlation between taste functions and clinical features in patients with Sjögren's syndrome (SS). METHODS: Sixty-three patients were divided into two groups: group A consisting of patients with primary or secondary SS of the European classification, and group B consisting of non-SS complaining of dry eye and mouth. RESULTS: Eighteen percent of the group A patients and 11% of the group B patients complained of taste disorders. Electrogustometric examination detected taste disorders in 27% of the group A patients and 38% of the group B patients, while the filter paper disc method showed taste disorders in 30% of group A and 40% of group B. In group A, unstimulated and stimulated salivary flows were correlated with the ability to discriminate taste analyzed by the filter paper disc method, but not with the taste electrogustometric threshold. Serum zinc concentration was not significantly correlated with taste disorders in either group. CONCLUSION: Our findings showed that SS patients presented taste disorders less frequently than previously reported, and we speculated that taste disorder found in SS patients were due to the salivary flow deficiency that might prevent substances from reaching the taste buds.

Adult↗

Taste discrimination between NaCl and KCl is disrupted by amiloride in inbred mice with amiloride-insensitive chorda tympani nerves.

The amiloride-sensitive salt transduction pathway is thought to be critical for the discrimination between sodium and nonsodium salts in rodents. In rats, lingual application of amiloride appears to render NaCl qualitatively indistinguishable from KCl. In this study, we tested four strains of mice for salt discriminability. In one strain (C57BL/6J), chorda tympani nerve (CT) responses to NaCl are attenuated by amiloride, and in the other three strains (BALB/cByJ, 129P3/J, DBA/2J) they are not. Under water-restriction conditions, these mice (7 mice/strain) were trained in a gustometer to lick for water from one reinforcement spout in response to a five-lick presentation of NaCl and to lick from another in response to KCl [salt concentration was varied (0.1-1 M) to render intensity irrelevant]. Mice were then tested with the stimuli dissolved in amiloride hydrochloride, and the latter was used as the reinforcer as well. Each concentration of amiloride (0.1-100 microM) was used on 2 separate days with control sessions interposed. Mice from all four strains were able to discriminate NaCl from KCl reliably. Amiloride impaired this discrimination in a dose-dependent fashion. Moreover, performance on NaCl trials appeared to be more affected by amiloride than that on KCl trials in all four strains. Thus, in contrast to the predictions based on CT recordings, discrimination in all four strains appeared to depend on the amiloride-sensitive transduction pathway, which, in the case of BALB/cByJ, 129P3/J, and DBA/2J (and perhaps C57BL/6 as well), may exist in taste buds innervated by nerves other than the CT.

Amiloride↗

[Morphofunctional study of the lingual papillae in cattle (Bos taurus)].

The morpho-functional and topographical features of the lingual papillae situated on the dorsal surface of the bovine tongue, were studied utilizing LM and SEM techniques. In the bovine species, the functional differentiation of the lingual papillae in their gustatory and mechanical modes, seems to be related to the position of the papillae rather than to their morphological features. The gustatory function predominates over the mechanical one on the caudal tract of the tongue body (lateral to the lingual torus and associated with circumvallate papillae). The gustatory function also involves the conical papillae situated on the caudal tract of the tongue body. This gustatory function is aided by additional anatomical structures: 1. The grooves situated on the rostro-lateral side of the conical papillae; 2. The microcraters located on the top of the fungiform papillae; and 3. The furrows of the circumvallatae papillae vallum. The contact between saliva soluble food particles and taste buds is aided and made more efficient by these structures. Furthermore, a large variety of conical papillae were observed, whereas no filiform papillae were noted.

Animals↗

Chemospecific deficits in taste detection after selective gustatory deafferentation in rats.

Electrophysiological data support the existence of sodium-specific taste receptors that appear to be limited to the anterior tongue. However, previous behavioral findings suggest that bilateral transection of the chorda tympani nerve (CTn) has minimal consequences on NaCl intake and preference. This study employed a conditioned avoidance procedure to measure detection thresholds to NaCl and sucrose both before and after bilateral transection of the CTn. Rats were trained to maintain spout contact in response to water presentations (70 microliters) and to avoid spout contact when a taste solution (70 microliters) was presented. In experiment 1, all rats (n = 3) showed statistically significant impairments in the detectability of NaCl after bilateral section of the CTn. The mean increase in the NaCl detection threshold was 1.41 log units. In contrast, sucrose threshold in these same rats was marginally affected by CTn section (mean increase = 0.22 log units). Experiment 2 (n = 4) replicated the findings of the first experiment. The mean increase in the NaCl detection threshold was 2.23 log units. Sucrose threshold in these rats was, again, only marginally affected by CTn section (mean increase = 0.83 log units). Histological examination of the anterior tongue from the rats in experiment 2 indicated that the CTn transections were complete. These findings reveal that the anterior oral receptive field (innervated by the CTn) containing only 15% of the total taste bud population is critical for the normal detection of NaCl.

Afferent Pathways↗

Responses from parabrachial gustatory neurons in behaving rats.

1. The responses of a total of 70 single neurons were recorded from the parabrachial nuclei (PBN) in awake rats. In 59 neurons, sapid stimuli (0.5 ml) elicited significant taste responses. Of these 59 neurons, 10 also had significant responses to water. The mean spontaneous rate of the taste neurons was 13.4 +/- 6.9 (SD) spikes/s. Of the remaining 11 neurons, 9 responded significantly only to water; 2 had no significant responses to the standard fluid stimuli. 2. Based on the magnitude of their response to our four standard stimuli, the taste neurons were classified as follows: 42 NaCl-best, 14 sucrose-best, 2 citric acid-best, and 1 QHCl-best. Of these, 25 responded only to one of four sapid stimuli; 20 of these specific cells responded only to NaCl. All the remaining 34 neurons responded to two or more of the four sapid stimuli, with NaCl and sucrose responsiveness dominant. For the 59 taste neurons, the mean entropy for the absolute value of the responses was 0.68; for the excitatory activity alone, it was 0.58. 3. The mean responses to NaCl and sucrose concentration series increased monotonically. Except at the lowest concentration, responses to citric acid also increased monotonically, but with a lower slope. Mean responses to QHCl, however, remained stable or even decreased with increasing concentration. Thus the power functions for the NaCl and sucrose intensity-response series were higher than those of citric acid and QHCl. 4. A hierarchical cluster analysis of 59 parabrachial neurons suggested four different categories: NaCl-best, sucrose-best, citric acid-best, and QHCl-best. These categories were less evident in the two-dimensional space produced by multidimensional analysis, because the positions of NaCl- and sucrose-best neurons formed a continuum in which neural response profiles change successively from sucrose-specific to NaCl-specific. 5. The results were consistent with previous anatomic and neurophysiological data suggesting convergence in the medulla of sensory input from receptors in the nasoincisor ducts (NID) and on the anterior tongue (AT). Taste buds in the NID respond preferentially to sucrose, whereas those on the AT respond more to NaCl.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

4-Aminopyridine reduces chorda tympani nerve taste responses to potassium and alkali salts in rat.

To study the potential role of potassium channels in the taste response to potassium salts, we applied 4-aminopyridine (4-AP) to the anterior rat tongue and recorded chorda tympani nerve taste responses to chemical stimuli. 4-aminopyridine is a pharmacological blocker that reduces potassium conductance through potassium channels in nerve and muscle. Summated neural responses to stimuli dissolved in water and in 4-AP were compared. Chemical stimuli included concentration ranges of KCl, KBr, KH2PO4, CsCl, RbCl, NH4Cl, NaCl and sucrose. The blocker reduced chorda tympani responses to KCl and other potassium salts, from 0.025 to 0.25 M. Responses to ammonium, rubidium and cesium salts also were reduced, in order of effectiveness that would be predicted from known ion selectivity properties of potassium channels. Responses to NaCl and sucrose were not reduced. Other channel blockers, including tetraethylammonium chloride (TEA), BaCl2 and quinidine, did not reduce the response to KCl. These are the first detailed reports of effects of potassium channel blockers on the peripheral, neural taste response. The results are consistent with a role for potassium channels in apical taste bud cell membranes in transduction for potassium salts.

4-Aminopyridine↗

Capsaicin modifies responses of rat chorda tympani nerve fibers to NaCl.

Single-fiber preparations of the rat chorda tympani (CT) nerve were used to study the mechanism of action of capsaicin on salt-taste transduction. Capsaicin selectively suppressed the responses to NaCl of the CT nerve fibers (N-fibers) that are sodium-specific (insensitive or poorly sensitive to potassium). Among the more broadly responsive, cation-sensitive fibers (E-fibers) there are two subtypes, both of which responded to capsaicin but in different ways ('enhanced' type and 'suppressed' type). In both N- and E-fibers, 5% ethanol (the vehicle for capsaicin) slightly reduced the response to 100 mM NaCl. The suppressive effect of capsaicin on the response of the N-type fibers to 100 mM NaCl was significantly stronger than the effect of 5% ethanol. The suppression lasted for at least 20 s after the simultaneous application of 100 p.p.m. capsaicin-100 nM NaCl. These results indicate that 100 p.p.m. capsaicin can modify the response of CT fibers to NaCl. The observed effect of capsaicin on gustatory fibers could be the net result of opposite suppressive and enhancing processes in the taste buds cells and excited intra- or extragemmal trigeminal nerve endings.

Animals↗

Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells.

The taste system, made up of taste receptor cells clustered in taste buds at the surface of the tongue and the soft palate, plays a key role in the decision to ingest or reject food and thereby is essential in protecting organisms against harmful toxins and in selecting the most appropriate nutrients. To determine if a similar chemosensory system exists in the gastrointestinal tract, we used immunohistochemistry and real-time polymerase chain reaction (PCR) to investigate which taste-signaling molecules are expressed in the intestinal mucosa. The PCR data showed that T1r1, T1r2, T1r3, alpha-gustducin, phospholipase Cbeta2 (PLCbeta2), and Trpm5 are expressed in the stomach, small intestine, and colon of mice and humans, with the exception of T1r2, which was not detected in the mouse and human stomach or in the mouse colon. Using transgenic mice expressing enhanced green fluorescent protein under the control of the Trpm5 promoter, we found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface epithelium of the colon, but these cells did not express T1r3 or PLCbeta2. In the duodenal glands, 43%, 33%, and 38% of Trpm5-expressing cells also express PLCbeta2, T1r3, or alpha-gustducin, respectively. The duodenal gland cells that coexpress PLCbeta2 and Trpm5 morphologically resemble enteroendocrine cells. We found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3 in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2. The data suggest that these duodenal cells are possibly involved in sensing amino acids.

Animals↗