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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↗
PubMed1986

[Contribution of stereochemistry to the study of the spatial organization of pharmacological receptors].

The important discovery by Pasteur of optical isomerism and the recent developments of stereochemistry showed that a complementarity exist between the geometry of molecules and their pharmacological receptors. The stereochemical bases and the principal configurational nomenclatures are briefly overviewed. The stereospecificity of the biological response and theories leading to an approach to stereochemical structures of main pharmacological receptors are developed. So, the biological activity of steroids is due to junctional modes of cycles and alpha or beta configurations of substituents. Acetylcholine has a skew conformation but it react by an anticlinal/anti-planar conformation with muscarinic receptor. To explain the difference in activity of adrenaline enantiomers, Easson and Stedman proposed a "three points" fixation to the adrenergic receptor. Dopaminergic receptor present a good degree of stereoselectivity: dopamine act by an anti-planar conformation in which the N-O distance is the same as in apomorphine (N-O10). The analgesic activity of morphinans is due to a cis junction of B and C cycles and to the stereoelectronic effect of the unshared lone pair on nitrogen. In the cyclamate sweeteners, some authors proposed for the sweet taste receptor a model with two points fixation (one acceptor and one donor) and two spatial barriers located at precise distances from this two sites. The stereoselectivity of molecules acting as substrates or inhibitors of enzymes is described. For example some oxazolidinone derivatives showed a selective inhibition toward monoamine oxidase A. Finally, the pharmacological activity falls often when molecules are administrated in racemic form. It seems that xenobiotics need to be dissymmetric for chiral recognition by biological systems.

Animals↗
PubMed1993

The taste system of the channel catfish: from biophysics to behavior.

Catfish, described as 'swimming tongues', are unique experimental models for studies of taste reception because of the extensive distribution of taste buds over their external body surface and within their oropharyngeal cavity. Both the extraordinary numbers of taste buds and their high sensitivity to amino acids have made it possible to perform in the same species: biochemical and biophysical studies of stimulus recognition and signal transduction; electrophysiological recordings of taste activity from receptor cells, afferent nerve fibers and CNS relays; and behavioral studies of taste-controlled food search, biting and mastication. The close correspondence of results obtained with these diverse experimental approaches has provided critical information concerning vertebrate gustation.

Amino Acids↗
PubMed1996

Characteristics of phosphatidic acid-containing lipoproteins which selectively inhibit bitter taste: high affinity to frog tongue surface and hydrophobic model membranes.

In previous studies (Katsuragi and Kurihara (1993) Nature 365,213--214; Katsuragi et al. (1995) Pharm. Res. 12,658--662) we showed that a lipoprotein composed of phosphatidic acid (PA) and beta-lactoglobulin (LG) selectively suppressed the taste responses to bitter substances without affecting those to other taste stimuli in the frog and man, while complexes composed of other lipids except for phosphatidylserine and LG had little inhibitory activity. In the present study, we found that the lipoproteins having inhibitory activity are adsorbed on the frog tongue surface, while those having no inhibitory activity are not adsorbed. We also examined adsorption of the lipoproteins on model lipid membranes coated on a quartz-crystal microbalance by measuring changes in its frequency. The lipoproteins having inhibitory activity were well adsorbed on the hydrophobic lipid membranes, while the lipoproteins having no inhibitory activity were little adsorbed on the membranes. It seems that receptor sites for bitter substances on the taste cell membranes are hydrophobic and those for other taste stimuli such as salts, acids and sugars are hydrophilic. Hence, the binding of PA-LG to hydrophobic sites of the receptor membranes will lead to selective inhibition of bitterness.

Adsorption↗
PubMed1995

Biogenic amines in the taste organ.

The presence and content of biogenic amines in taste disk-bearing fungiform papillae of the frog, Rana esculenta, the only available model of an isolated taste organ, were verified by means of HPLC. Fungiform papillae were found to contain measurable amounts of serotonin, epinephrine and norepinephrine. The amounts of serotonin and epinephrine were significantly higher in fungiform papillae than in the general mucosa of the tongue. Moreover, the epinephrine content of fungiform papillae was found to differ across the tongue, in accordance with previous physiological studies showing an inhomogeneous response of different tongue regions to taste stimuli. Ultrastructural and histochemical investigations confirmed the presence of catecholamine and serotonin. The latter was found to be contained mainly in the basal cells of the frog taste disk. These results extend previous qualitative data on the presence of biogenic amines in taste chemoreceptors.

Animals↗
PubMed1998

The role of innervation in the development of taste buds: insights from studies of amphibian embryos.

Amphibian embryos have long been model organisms for studies of development because of their hardiness and large size, as well as the ease with which they can be experimentally manipulated. These particular advantages have allowed us recently to test the role of innervation in the development of vertebrate taste buds using embryos of an aquatic salamander, the axolotl. The predominant model of taste bud genesis has been one of neural induction, in which ingrowing sensory neurites induce taste bud differentiation in the epithelium that lines the mouth and pharynx. However, when we prevented embryonic sensory neurons from contacting the oropharyngeal epithelium by using transplantation or tissue culture techniques, we found that taste bud differentiation was independent of nerve contact. Additionally, using similar types of experimental manipulations, we have recently shown that taste bud differentiation is not a result of interactions of the oropharyngeal epithelium with craniofacial mesenchyme. Surprisingly, we found that although taste bud genesis occurs very late in embryonic development, it is an intrinsic feature of the presumptive oropharyngeal epithelium extremely early, in fact as early as the completion of gastrulation. These data have prompted us to propose a new model for the development of amphibian taste buds: (i) The presumptive oropharyngeal epithelium is specified by the time gastrulation is complete; (ii) Subsequently, a distributed population of taste bud progenitors is set up within this epithelium via local cell-cell interactions. These progenitor cells give rise to taste buds, which are distributed throughout the mouth and pharynx. How widely applicable this model might be for the genesis of taste buds in other vertebrates remains to be seen. However, since it is likely that the taste system of axolotls more closely resembles the ancestral state from which both the amphibian and mammalian taste systems have evolved, it is possible that many of the same developmental mechanisms that give rise to amphibian taste buds are also used to generate the receptor organs in mammals.

Ambystoma↗
PubMed1989

Lipid characterization and 14C-acetate metabolism in catfish taste epithelium.

The catfish, Ictalurus punctatus is an important model system for the study of the biochemical mechanisms of taste reception. A detailed lipid analysis of epithelial tissue from the taste organ (barbel) of the catfish has been performed. Polar lipids account for 62 +/- 1% of the total, neutrals for 38 +/- 1%. Phosphatidyl-cholines, serines and ethanolamines are the major constituents of the polar fraction. Plasmalogen concentration is high relative to that of non-neural tissues. [14C]-Acetate is incorporated into cell lipid fractions after incubation of barbel tissue at 37 degrees C for 60 min. Percentage amounts of most lipids change with time during this in vitro incubation. The phospholipids are the most metabolically active fractions. This work yields information for continuing reconstitution experiments and indicates that the taste epithelium of this important model system is a metabolically active tissue capable of supporting lipid turnover/synthesis.

Acetates↗
PubMed1988

Effects of magnetic fields from underwater electrical cutting on in vitro corrosion of dental amalgam.

Metallic taste has been reported from divers working with underwater electric welding and cutting. An in vitro model was designed to simulate the intraoral situation of the divers with respect to the magnetic field. Potentiostatic analyses were performed on amalgam samples exposed to AC and DC magnetic fields. Morphologic changes were analyzed using differential interference light microscopy and scanning electron microscopy. Chemical changes on the surface of the amalgam samples were analyzed with secondary ion mass spectrometry. Results demonstrated that dental amalgams exposed to a specific AC magnetic field underwent morphologic and chemical changes in the superficial amalgam layers.

Corrosion↗
PubMed1994

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

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

Amiloride↗
PubMed1989

The cell biology of vertebrate taste receptors.

New technologies in neurophysiology and ultrastructural research are bringing about rapid advances in our understanding of taste, particularly at the cellular level. The model of chemosensory processing in the taste bud presented here can now be explored in great detail. The synaptic organization of the taste bud indicates a potential for intriguing peripheral integrative mechanisms, including cross-talk between taste cells, summation of chemoreceptor responses by interneurons (basal cells) in the taste bud, and centrifugal control of taste buds via efferent input from the CNS. Figure 2 summarizes these findings. The existence of voltage-gated ionic channels on taste cells and their unequal distribution in apical and basolateral membrane suggests mechanisms for chemosensory transduction: A primary event in the transduction process for many taste stimuli is likely to be the closure of apical potassium channels, thus leading to a depolarizing receptor potential. The closure of these apical potassium channels is probably mediated via cyclic nucleotides or intracellular Ca2+.

Animals↗
PubMed1980

The effect of social cues on the eating behavior of obese and normal subjects.

Schachter's externality hypothesis suggests that overweight individuals are more likely to be induced to eat by salient external cues than normal weight individuals. While a range of studies have demonstrated the plausibility of this hypothesis in the case of sensory stimuli (e.g., taste cues), there is little evidence that the hypothesis applies to social stimuli. The current study examines this latter proposition by exposing male and female, overweight and normal weight subjects to a same-sex or opposite-sex peer model. Under the guise of engaging in a taste experiment, the subjects were either exposed to a model who tasted no crackers (no eat), one cracker (low eat), or twenty crackers (high eat). In addition, control model-absent conditions were also run for purposes of establishing baseline eating rates. If the externality hypotheses were to prevail in social domains, one would expect overweight subjects to be more prone to model the cracker-eating behavior of the peer than normal weight individuals. However, the findings indicate that all subject groups regardless of weight evidence a rather clear modeling effect and all subjects evidence social inhibition effects on their eating behavior as well. Several intriguing interactions among subject sex, model sex, subject weight, and social condition were also found. The discussion explores the relevance of an externality model of overweight eating in social domains, and focuses upon the interesting and somewhat distinct pattern of socially mediated eating exhibited by overweight females.

Cues↗
PubMed1978

Taste profiles from single human taste papillae.

Earlier psychophysical research on single human fungiform taste papillae employed a procedure which limited subjects to selecting only one taste to describe the sensations they experienced. That procedure precludes the possibility of determining whether single papillae can mediate complex tastes, i.e., tastes consisting of more than one sensation experienced simultaneously. By using highly trained subjects and allowing them freedom to describe all sensations simultaneously elicited by a given taste stimulus, single papilla taste profiles were obtained. It is suggested that obtaining taste profiles may increase the utility of single papillae as models for study of the taste system.

Adult↗
PubMed1993

Statistical analysis of neural organization.

1. The responses of 32 taste neurons in the solitary nucleus of the rat to 12 stimuli were analyzed with multidimensional scaling (MDS) and cluster analysis (CA) procedures. These analyses of empirical taste data were compared with similar analyses of two model data sets of known configuration to help clarify the implications of these methods commonly used in forming conclusions about the organization of the taste system. 2. To relate to possible conclusions about groupings in taste, both model data sets were chosen as the best possible examples of ungrouped data, the first being completely regular (in the form of a checkerboard) across the taste space, the second randomly arranged. The analysis of the present empirical data appear to be similar to the present ungrouped models, more so the random than the regular model, in the sense that all are amenable to grouping. 3. Because of the similarity of these model MDS and CA solutions to the present empirical solutions and to most published analyses of this sort, the idea is suggested that the appearance of the plots per se for empirical data does not support the conclusion of grouping. And, technically, MDS and CA do not have the statistical power to provide conclusions about issues of neural organization. 4. MDS and CA analyses have two very powerful roles relating to their ability to disclose the hidden organization of complex data sets; they may lend support for or refute theories about the data sets developed from other considerations, and may help generate theories for further consideration. The question of groupings is only one of many such issues. 5. Because data in the present and other reports are quite adequately accounted by MDS solutions of low dimensionality, it is suggested that their organization is characterized as continuous (i.e., rather than belonging to several disjoint spaces). 6. The use of correlations as distance measures in MDS and CA procedures distorts the spatial solutions, making analysis by visual inspection misleading. For example, using correlations, the true or natural spatial arrangements of data sets are probably less circular or spherical than shown in published MDS solutions. Also they are probably more evenly distributed across the space in the sense that the points are actually more concentrated toward the centers of the spaces; this may have strong influences on interpretations of the general form of the solutions. CA solutions can be influenced in analogous fashion. These problems of distortion of the solutions can be avoided with use of direct, linear estimates of distances. (ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMedDate not supplied

Sweet and bitter taste: structure and conformations of two aspartame dipeptide analogues.

The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.

Aspartame↗