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PubMed1994

Enhancement of salt intake by choline chloride.

The ingestion of salt (NaCl) in most societies far exceeds levels that are considered necessary and safe. To reduce salt intake, a rat model of salt taste acceptance was created to identify novel, more palatable salt substitutes/enhancers. To induce salt craving, male Sprague-Dawley rats were placed on a low-salt diet and injected weekly (SC) with either 100 mg/kg of deoxycorticosterone acetate (DOCA) or its vehicle, peanut oil. Following 16 h of fluid deprivation, intake was evaluated in a one-bottle acceptance procedure. The DOCA-injected animals consumed large volumes of salt-containing solutions (up to 120 ml in 2 h) and showed sensitivity to and specificity for the salt taste (generally lacking acceptance of dextrose, KCl, ammonium chloride, and water solutions). Using this model, choline chloride was identified as having salt taste-enhancing properties. Choline chloride (0.1-0.7%) significantly enhanced the intake of a dilute salt solution (0.1%). The relevance of the rat model was demonstrated in human taste trials; choline chloride enhanced the palatability of and preference for foods containing this compound. The results of the present experiments support the use of this animal model for evaluating compounds for salt-like taste qualities and suggest that choline chloride will be an effective salt taste enhancer in man.

Animals↗
PubMed1983

Interaction of conformationally flexible agonists with the active site of sweet taste. A study of arylureas.

The conformation of tolylureas has been studied by means of X-ray diffraction, NMR spectroscopy, and semiempirical quantum-mechanical calculations. The flat shape of meta and para isomers allows a good interaction with the model sites for bitter and sweet taste, respectively, whereas the ortho isomer cannot fit the sites because of the relative arrangements of the aryl and amide planes and because of poor hydrophobic interactions. The consistency of the conformational results with the sweet taste model site, previously proposed by the authors, is emphasized by the good fit of dulcine, a sweeter para-substituted arylurea.

Humans↗
PubMed1982

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

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

Alanine↗
PubMed1988

Ab initio molecular electrostatic potentials of perillartine analogues: implications for sweet-taste receptor recognition.

A model for the recognition of the perillartine analogues has been determined from a consideration of the molecular electrostatic potentials calculated at the ab initio 3-21G level for a select set of biologically active analogues. The model stresses the importance of two regions of negative electrostatic potential. One region, near the oxime moiety, does not vary in shape or value with substitution in the hydrocarbon domain. A second region in the hydrocarbon domain varies in depth, extension, orientation, and shape, depending on the nature of the substituent. The depth, relative position, and orientation of this latter region in the most potent systems (the 1,4-cyclohexadiene analogue and its p-methyl derivative) serve as the basis for the optimum recognition pattern of these analogues. The rank order of taste potencies is in general agreement with predictions based on this model. In addition, some conclusions are drawn concerning the receptor-analogue interaction as well as the electrostatic features of the receptor.

Cyclohexenes↗
PubMed1987

Taste and bulimia.

Binge-eating episodes in bulimia often involve sweet or fat-containing foods. Sensory perceptions and preferences for sweetness and fat content were examined in 16 normal-weight women with a diagnosis of DSM IIIR bulimia and in 16 normal-weight volunteer controls. Taste stimuli were 15 semi-liquid mixtures of dessert-type soft white cheese ("fromage blanc") containing 0, 3 or 7 grams of fat per 100 g, and sweetened with 1, 5, 10, 20, or 40% sucrose (wt./wt.). The subjects used 9-point category scales to rate the perceived sweetness and fat content of the stimuli, and assigned a pleasantness (hedonic) rating to each sample. Taste preferences were modelled using the Response Surface Method (RSM). Mean estimates of sweetness intensity and fat content were generally similar for bulimic patients and controls. In contrast, profiles of taste preference differed significantly between groups. Optimal stimulus sweetness was 15% sucrose wt./wt. for bulimic patients and only 9% for controls, while optimal fat levels were lower for bulimic patients relative to controls. The present data are consistent with previous reports that patients with eating disorders crave sweetness but show reduced sensory preferences for fat-containing foods.

Adult↗
PubMed1984

The active ion transport properties of canine lingual epithelia in vitro. Implications for gustatory transduction.

The electrophysiological properties of the dorsal and ventral canine lingual epithelium are studied in vitro. The dorsal epithelium contains a special ion transport system activated by mucosal solutions hyperosmotic in NaCl or LiCl. Hyperosmotic KCl is significantly less effective as an activator of this system. The lingual frenulum does not contain the transport system. In the dorsal surface it is characterized by a rapid increase in inward current and can be quantitated as a second component in the time course of either the open-circuit potential or short-circuit current when the mucosal solution is hyperosmotic in NaCl or LiCl. The increased inward current (hyperosmotic response) can be eliminated by amiloride (10(-4) M). The specific location of this transport system in the dorsal surface and the fact that it operates over the concentration range characteristic of mammalian salt taste suggests a possible link to gustatory transduction. This possibility is tested by recording neural responses in the rat to NaCl and KCl over a concentration range including the hyperosmotic. We demonstrate that amiloride specifically blocks the response to NaCl over the hyperosmotic range while affecting the KCl response significantly less. The results suggest that gustatory transduction for NaCl is mediated by Na entry into the taste cells via the same amiloride-sensitive pathway responsible for the hyperosmotic response in vitro. Further studies of the in vitro system give evidence for paracellular as well as transcellular current paths. The transmural current-voltage relations are linear under both symmetrical and asymmetrical conditions. After ouabain treatment under symmetrical conditions, the short-circuit current decays to zero. The increase in resistance, though significant, is small, which suggests a sizeable shunt pathway for current. Flux measurements show that sodium is absorbed under symmetrical conditions. Mucosal solutions hyperosmotic in various sugars also induce an amiloride-sensitive inward current. In summary, this work provides evidence that the sodium taste receptor is most probably a sodium transport system, specifically adapted to the dorsal surface of the tongue. The transport paradigm of gustation also suggests a simple model for electric taste and possible mechanisms for sweet taste.

Amiloride↗
PubMed1991

Gustatory neural coding in the monkey cortex: stimulus intensity.

1. We analyzed the activity of single neurons in gustatory cortex of alert cynomolgus monkeys in response to a range of stimulus intensities. Chemicals were deionized water, fruit juice, and several concentrations of the four prototypical taste stimuli: 10(-3)-1.0 M glucose, 10(-3)-1.0 M NaCl, 10(-4)-3 x 10(-2) M HCl, and 10(-5)-3 x 10(-3) M quinine HCl. 2. Taste-evoked responses could be recorded from a cortical gustatory area that measured 2.5 mm in its anteroposterior extent, 6.0 mm dorsoventrally, and 3.0 mm mediolaterally. Taste-responsive cells constituted 62 (3.7%) of the 1,661 neurons tested. Nongustatory cells gave responses associated with mouth movement (10.1%), somatosensory stimulation (2.2%), and approach or anticipation (0.9%). 3. Intensity-response functions were determined across 62 gustatory neurons. Neural thresholds for each stimulus quality conformed well to human psychophysical thresholds. Mean discharge rate was a direct function of stimulus concentration for glucose, NaCl, and quinine HCl. The most effective of the basic stimuli was glucose. 4. Power function exponents were calculated from the responses of neural subgroups most responsive to each basic stimulus. Those for glucose, NaCl, and quinine were within the range of psychophysically derived values. Thus the perceived intensity of each basic quality is presumably based on the activity of the appropriate neural subgroup rather than on the mean activity of all taste cells. 5. The mean breadth-of-tuning (entropy) coefficient for 62 gustatory neurons was 0.65 (range, 0.00-0.98). 6. There was no clear evidence of chemotopic organization in the gustatory cortex. 7. An analysis of taste quality indicated that sweet stimuli evoked patterns of activity that were clearly distinct from those of the nonsweet chemicals. Among the latter group, NaCl was differentiable from HCl and quinine HCl, whose patterns were closely related. 8. The response characteristics of cortical taste cells imply gustatory thresholds and intensity-response functions for the nonhuman primate that conform well to those reported in psychophysical studies of humans, reinforcing the value of this neural model for human taste intensity perception.

Action Potentials↗
PubMed1979

Salt taste adaptation: the psychophysical effects of adapting solutions and residual stimuli from prior tastings on the taste of sodium chloride.

The paper reviews how adaptation to sodium chloride, changing in concentration as a result of various experimental procedures, affects measurements of the sensitivity, intensity, and quality of the salt taste. The development of and evidence for the current model that the salt taste depends on an adaptation level (taste zero) determined by the sodium cation concentration is examined and found to be generally supported, despite great methodological complications. It would seem that lower adaptation levels elicit lower thresholds, higher intensity estimates, and altered quality descriptions with predictable effects on psychophysical measures.

Adaptation, Physiological↗
PubMed1994

Application of serial sectioning and three-dimensional reconstruction to the study of taste bud ultrastructure and organization.

The lingual taste buds of mammals are complex organs containing dozens of cells of varying morphology and numerous nerve fibers that are intermingled among the cellular processes. Some of the taste bud cells form synaptic contacts with these nerve fibers. Important questions remain to be answered regarding the structure and function of the cells of various types within taste buds and the means by which responses to gustatory stimuli are transmitted to the nerve fibers that communicate with the brain. Using both conventional and high voltage electron microscopy, we have examined serially sectioned taste buds from the tongues of mice and rabbits in order to address these issues and to obtain more complete information than that available from sampling of sections. The technique of computer-assisted 3-D reconstruction was used to generate models of whole taste buds and individual cellular and neural elements within taste buds from the serial sections. Analysis of serially sectioned taste buds from mice and rabbits has revealed that in both of these species relatively few (30% or less) of the cells within the taste buds form synaptic contacts with nerve fibers. In the foliate taste buds of rabbits, all of the cells that are presynaptic to nerve fibers are of a single morphological type (type III). The cells that are presynaptic to nerve fibers within the taste buds of mice are morphologically diverse. A pattern of synaptic connectivity exists within murine taste buds such that a given nerve fiber receives synaptic input only from taste cells that are ultrastructurally similar. In the taste buds of both mice and rabbits, we have observed both divergence and convergence of synaptic input from the putative taste receptor cells onto nerve fibers, suggesting that at the level of the taste bud there is some integration of the information generated by individual receptor cells. In addition to typical chemical synapses, other cytoplasmic specializations (such as subsurface cisternae and atypical mitochondria) may be involved in interactions between taste bud cells and nerve fibers.

Animals↗
PubMed1995

Estimation of the junctional resistance between electrically coupled receptor cells in Necturus taste buds.

Junctional resistance between coupled receptor cells in Necturus taste buds was estimated by modeling the results from single patch pipette voltage clamp studies on lingual slices. The membrane capacitance and input resistance of coupled taste receptor cells were measured to monitor electrical coupling and the results compared with those calculated by a simple model of electrically coupled taste cells. Coupled receptor cells were modeled by two identical receptor cells connected via a junctional resistance. On average, the junctional resistance was approximately 200-300 M omega. This was consistent with the electrophysiological recordings. A junctional resistance of 200-300 M omega is close to the threshold for Lucifer yellow dye-coupling detection (approximately 500 M omega). Therefore, the true extent of coupling in taste buds might be somewhat greater than that predicted from Lucifer yellow dye coupling. Due to the high input resistance of single taste receptor cells (> 1 G omega), a junctional resistance of 200-300 M omega assures a substantial electrical communication between coupled taste cells, suggesting that the electrical activity of coupled cells might be synchronized.

Animals↗
PubMed1992

Gustatory neural coding in the monkey cortex: L-amino acids.

1. Single-neuron activity in the primary gustatory cortex of the alert cynomolgus monkey (Macaca fascicularis) was analyzed in response to a range of taste stimuli. Tastants included the four prototypical stimuli (glucose, NaCl, HCl, and quinine), fruit juice, and 12 amino acids selected for their chemical characteristics, nutritional significance, and biological importance, as well as for the availability of human psychophysical data on their perceived qualities. 2. Taste-evoked responses could be recorded from a cortical area that measured 3.5 mm in its anteroposterior extent, 2.0 mm mediolaterally, and 6.0 mm dorsoventrally. Gustatory cells constituted 4.8% of the 1,129 neurons tested. Nongustatory cells gave responses associated with mouth movements (11.1%), somatosensory stimulation (3.8%), approach or anticipation of the taste stimulus (2.2%), and tongue extension (0.4%). 3. The most effective taste stimuli were those with qualities that humans describe as salty or sweet: NaCl, monosodium glutamate, glucose, proline, glycine, and fruit juice. The least effective tastants were those rated bitter or insipid: tyrosine, tryptophan, phenylalanine, and leucine. Accordingly, 79% of the gustatory neurons responded best to glucose (46%) or NaCl (33%) among the basic stimuli; only 19% responded best to quinine (13%) or HCl (6%). One cell (2%) responded exclusively to fruit juice. 4. Cortical gustatory neurons showed a moderate breadth of sensitivity, with a mean breadth of tuning coefficient of 0.71 across 54 cells. There was no evidence of chemotopic organization in the taste cortex. 5. The taste quality of each stimulus was inferred from the relative similarity of the profiles they evoked. The clearest distinction among stimuli was between those that humans characterize as sweet versus those with other qualities. Several amino acids that have dominant sweet (glycine and proline), salty (arginine and monosodium glutamate), sour (tryptophan), or bitter (phenylalanine) components to humans evoked activity profiles that were associated with those of the appropriate prototypical stimuli. Others (cysteine and lysine) were not closely related to any single prototype. 6. Conclusions based on the responses of cortical cells in the monkey are in close agreement with those that derive from human psychophysical studies of L-amino acids, reinforcing the value of this neural model for human taste perception.

Amino Acids↗
PubMed1996

Basolateral amiloride-sensitive Na+ transport pathway in rat tongue epithelium.

1. Experiments were conducted to test for the presence of basolateral Na+ channels in the rat lingual epithelium. Researchers have proposed a model in which some lingual taste cells have Na+ channels in the basolateral membrane. That model is designed to account for the portion of the neural taste response and the portion of the transepithelial short-circuit current (Isc) in vitro that are insensitive to mucosal amiloride; some Na+ would diffuse across the tight junction into the cell via this lateral pathway, and would be transported out of the cell by Na+ pumps in the basal membrane. The model could also account for the differential effect of mucosal amiloride on Na+ salts of various anions, in which the neural taste responses to Na+ salts with anions larger than Cl- are more sensitive to mucosal amiloride than is the taste response to NaCl. 2. Voltage-clamp data were obtained from an in vitro preparation of the anterior-dorsal rat tongue epithelium in which the connective tissue was removed by enzyme digestion. Isc in a modified Ussing chamber was reduced by amiloride in the submucosal solution. 3. The pattern of sensitivity to submucosal amiloride differed in several respects from the pattern for mucosal amiloride. The inhibition constant (Ki) was 52 microM amiloride concentration, higher than for the apical amiloride-sensitive Na+ channel. The selectivity for Na+ over K+ was much less than for the response to mucosal amiloride; with 0.5 M NaCl or KCl on the mucosal side, the ratio of inhibition for the NaCl response to inhibition for the KCl response varied between 1 and 3. 4. As the concentration of NaCl in the mucosal solution was varied, submucosal amiloride caused little inhibition of Isc for mucosal NaCl below isosmotic concentration, with the percent inhibition increasing as mucosal salt concentration increased. With 0.5 M sodium gluconate in the mucosal solution, there was very little inhibition due to submucosal amiloride. 5. The results support the presence of amiloride-sensitive Na+ channels in the basolateral membranes of the dorsal tongue epithelium in rat, and are consistent with the proposed model in which these channels are present in taste cells.

Amiloride↗
PubMed1993

Gustatory neural coding in the monkey cortex: the quality of sweetness.

1. We analyzed the activity of single neurons in gustatory cortex of alert cynomolgus monkeys in response to the four basic taste stimuli and to a range of chemicals, all of which are predominantly sweet to humans. 2. We recorded taste-evoked responses from a cortical area that measured 4.0 mm in its anteroposterior extent, 5.6 mm dorsoventrally and 2.2 mm mediolaterally. Taste-responsive neurons constituted 4.7% of the 3,066 neurons tested in the course of 66 recording tracks. Nongustatory cells included those responsive to mouth movement (34.1%), tongue touch (1.9%), stimulus approach (0.7%), and tongue extension (0.5%). The functions of 58.2% of the cells we isolated could not be determined. 3. The mean breadth of tuning of these cortical taste neurons was a moderate 0.59 (range 0.00-0.93). 4. There was no evidence that taste cells with similar functional attributes were clustered in the cortex, i.e., there was no apparent topographic organization of taste qualities. 5. A taste space was generated from the correlations among patterns of neural activity evoked by the stimulus array. Within the space, NaCl was most isolated from other stimuli; the profiles elicited by HCl, quinine HCl, and water were all moderately intercorrelated and were clearly distinct from the cluster of sweet stimuli. 6. The 19 sweet chemicals formed a coherent cluster centered on the simple carbohydrates (glucose, fructose, sucrose, maltose) and sorbitol. Nearest this core were calcium cyclamate, aspartame, and cran-raspberry juice. In the next concentric ring were acesulfame potassium, xylose, xylitol, sorbose, polycose, and myoinositol. Increasingly distant from the sugars were sodium saccharin, stevioside, neohesperidin DHC, L-tryptophan and monellin. 7. We compared these results with those of a human psychophysical study of sweet stimuli. Using the position of glucose as a reference, we measured the distances to all other stimuli that were common to the two studies (n = 15). The correlation between the human psychophysical data and those derived from evoked activity in the macaque cortex was +0.82. 8. The high correlation between human psychophysical and macaque electrophysiological data implies that the subtle distinctions among stimuli that are predominantly sweet are quite similar for these two species and reinforces the value of this neural model for human taste perception.

Action Potentials↗
PubMed1994

Dissociation between conditioned taste aversion and radial maze learning following seizure-induced multifocal brain damage: quantitative tests of serial vs. parallel circuit models of memory.

Multivariate analyses between conditioned taste aversion (CTA) and radial maze acquisition (RMA) scores and percentages of neuronal dropout within thalamic and telencephalic structures were completed for rats in which overt seizures had been evoked following a single systemic injection of lithium/pilocarpine. Despite multifocal damage, only the amount of damage within the hippocampus (CA1) and the basolateral amygdala was most strongly associated with attenuated CTA, whereas damage within the mediodorsal thalamus was primarily associated with RMA. There was no significant correlation between CTA or RMA. Multiple regression analyses for specific Paxinos and Watson structures and their traditional aggregates supported more precise delineation of neuronal substrates of learning/memory and a multimodal (parallel) model for these processes.

Animals↗
PubMed1998

Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans.

Psychophysical cross-adaptation experiments were performed with two carbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners, acesulfame-K (MOD) and dulcin (DUL). Seven subjects were asked to match concentrations that elicited the same intensity as a sucrose reference (30 g/l). Cross-adaptation levels were calculated as the ratio of isointense concentrations measured for a given stimulus before and under adaptation. On average, cross-adaptation between SUC and FRU is low and apparently reciprocal. By contrast, cross-adaptation between SUC and MOD is clearly non-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MOD fails to adapt SUC (2%, P < 0.79). Significant and reciprocal cross-enhancement is observed between DUL and MOD (approximately -20%, P < 0.03), and also between SUC and DUL (approximately -15%, P < 0.08). In parallel, molecular modeling of the four tastants was performed in order to look for the 12 common binding motifs that were isolated on 14 other tastants in a previous study. SUC and FRU each display 10 out of the 12 binding motifs, whereas DUL and MOD only display four and five distinct motifs respectively and do not have any motif in common. Experimental cross-adaptation levels seem to correlate well with the number of motifs that molecules have in common. FRU and SUC share a majority of binding motifs and correlatively show mutual cross-adaptation. Four motifs of MOD are found among the 10 motifs of SUC, which may explain why SUC cross-adapts MOD but not vice versa. By contrast, DUL and MOD do not share any motif and do not cross-adapt. The various molecular mechanisms that may be responsible for cross-adaptation and/or cross-enhancement are discussed in light of our results.

Female↗
PubMed1989

The B6.SW bilineal congenic sucrose octaacetate (SOA)-taster mice.

SWR/J inbred mice (Tasters) reliably avoid, whereas C57BL/6J inbred mice (Nontasters) are indifferent to, sucrose octaacetate (SOA) at certain concentrations. From these strains we have developed a set of bilineal congenic Taster mice. Approximately 4000 mice, from 2 isogenic and 12 segregating generations, were tested in a program designed to evaluate genetic models for SOA tasting during development of congenic strains. The criterion phenotype was avoidance or nonavoidance in preference tests of the bitter tastant SOA at concentrations of 10(-4) and 10(-5) M. Across the 12 segregating generations, the results were consistent with Mendelian expectations for a single autosomal locus with complete dominance of the Taster phenotype. The breeding program produced 12 replicate B6.SW lines containing the taster allele on the B6-Nontaster genomic background. The congenic Taster mice may facilitate a functional analysis of the sense of taste.

Animals↗
PubMed1991

Specificity of mono- and divalent salt transduction mechanisms in frog gustation evidenced by cobalt chloride treatment.

1. Discrimination among stimuli with similar physical properties represents a formidable problem in sensory neurophysiology. The differential effect of cobalt chloride treatment on gustatory responses to monovalent and divalent salts may help to explain aspects of how the frog gustatory system encodes these stimuli. 2. Gustatory neural responses recorded from the glossopharyngeal nerve to divalent stimuli (CaCl2 and MgCl2) were inhibited by CoCl2 treatment, whereas monovalent responses (NaCl and KCl) were greatly augmented. Both effects were highly significant and completely reversible. 3. Intracellular recordings from the gustatory receptor cells, which synaptically initiate the impulses in the glossopharyngeal afferents, imply that these neural events are not a simple reflection of the receptor potential magnitude. Monovalent receptor potentials magnitudes (millivolts of depolarization) were enhanced by cobalt chloride, but receptor potentials to divalent stimuli were not inhibited. Rather they were either unaffected (MgCl2) or augmented (CaCl2). 4. Membrane resistance change during salt stimulation with cobalt chloride treatment followed the qualitative pattern observed with the neural response. Membrane resistance (in megohms) of the receptor cell was greater for divalent stimuli with cobalt treatment compared with divalent stimuli alone. Membrane resistance changes for monovalent stimuli were less with cobalt treatment compared with monovalent stimuli alone. These observations indicate that the glossopharyngeal neural response is not a simple reflection of the magnitude of the receptor potential but must be considered in conjunction with membrane resistance as an indicator of synaptic transmission. 5. These data were interpreted in terms of leading models of salt taste transduction, i.e., adsorption theories, phase boundary theories, and the direct penetration theories. Relevant mechanistic considerations for salt taste transduction in the frog include binding by divalents to membrane surface changes and amiloride-sensitive monovalent cation channels. It was concluded that the surface potential alone was not a critical variable in the mechanism of cobalt chloride alteration of salt responses.

Afferent Pathways↗