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Mixtures of substances with similar tastes. A test of a psychophysical model of taste mixture interactions.

When substances of similar taste are mixed, the mixture can show suppression or synergism. That is, the perceived intensity of the mixture can be less than or greater than the sum of the perceived intensities of the components. In the present study, these departures from simple additivity could be predicted from the psychophysical functions relating tast intensity to stimulus concentration of the unmixed components. Psychophysical functions are said to show compression when successive increments in concentration produce progessively smaller increments in perceived intensity and to show expansion when successive increments in concentration produce progressively larger increments in perceived intensity. Suppression resulted from mixtures of substances with compressed psychophysical functions, and synergism resulted from mixtures of substances with expanded functions.

Adult

A model for the stimulation of taste receptor cells by salt.

A taste cell mucosal surface is regarded as a planar region containing bound anionic sites and openings to ionic channels. It is assumed that the bulk aqueous properties of the exterior phase are not continuous with the surface but terminate at a plane near the surface. The region between the (Stern) plane and the membrane is regarded as having a lower dielectric constant than bulk water. This fact admits the possibility of ion pair formation between fixed sites and mobile cations. Mobile ion pairs entering the region may also bind to a fixed anionic site. Thus, it is assumed that mobile cations and ion pairs are potential determining species at the surface. Binding cations neutralizes surface charges, whereas binding mobile ion pairs does not. This competition accounts for the observed anion effect on stimulation of tast receptors by sodium salts. The potential profile is constructed by superimposing the phase boundary potentials with an ionic diffusion potential across the membrane. The model accounts for the anion effect on receptor potential, pH effects, the reversal of polarity when cells are treated with FeCl3, and the so-called "water reponse," depolarization of the taste cell upon dilution of the stimulant solution below a critical lower limit. The proposed model does not require both bound cationic and anionic receptors, and further suggests that limited access to a Stern-like region continuous with membrane channels may generally serve to control transport of ions.

Acetates

Physicochemical studies of taste reception. III. Interpretation of the water response in taste reception.

The model membrane composed of a Millipore filter paper and the total lipids from bovine tongue epithelium or phosphatidylcholine from egg yolk simulated well the water response of a living taste cell, The water response observed with the model membrane adapted to various salt solutions was interpreted in terms of changes in electric potential at the membrane-solution interface, i.e. the water response was attributed to the e.m.f. change produced by diffusion of the electrolytes dissolved in (or adsorbed on) the membrane surface into the bulk solution. The water response of the frog tongue was also investigated by measuring the neural response of the glossopharyngeal nerve. The results obtained were consistent with the mechanism proposed in the present paper. The response of the frog to Ca2+ was examined under the condition where the water response was suppressed, and it was concluded that the water response of the frog is different from the response to Ca2+.

Animals

Concept of neuron types in gustation in the rat.

1. In taste neurophysiology, from Pfaffmann's (49, 50) pioneering work until the present, the possibility of types of neurons corresponding in some sense with the "primary" taste qualities of Henning (33) has been entertained: recently types of gustatory neurons in peripheral nerves have been established according to which of the four classical stimuli is the "best stimulus." However, considerable variation occurs in the response profiles within neurons classified as belonging to the same type. The purpose of this research is to determine, using mathematical techniques where appropriate, if the within-type variation is spurious or, instead, indicates the absence of a typology of taste neurons. The data used were counts of the spike discharges of 50 individual taste neurons in the nucleus of the solitary tract of the rat, evoked by 32 diverse chemical stimuli. 2. Using as input the matrix of Pearson r correlation coefficients calculated for the responses of all pairings of neurons to all stimuli, multidimensional scaling analysis revealed a two-dimensional space in which no clear groupings of neurons occurred. 3. In a hierarchical cluster analysis of the neuron response profile similarities, no evidence of grouping was found, suggesting a more-or-less continuous variation among neurons. 4. When the organization of the 32 stimuli utilized was studied by the same techniques, no clear evidence for stimulus types was found, although the possibility of two stimulus types--"sweet" and "nonsweet"--was raised. 5. Construction of a joint neuron-stimulus space supported a spatial model of taste neuron-stimulus interaction, while analysis of the number and pattern of high correlations among neurons--even after allowance for attenuation due to measurement error--failed to support the notion of types of taste neurons with identical response profiles. 6. Aspects of the logical role of types of neurons in gustatory coding were discussed, and the results and methods of the present investigation were related to classification schemes for neurons in general. Suggestions for a formal taxonomy of neurons were given. 7. It should be emphasized that the present study and conclusions are of second-order, CNS neurons, whereas the studies advocating the presence of neurons types were of peripheral neurons. Taken together, the implication to be drawn from these studies is that if neural types do exist in peripheral taste nerves, the typology is lost at the first synapse and is thus unavailable to the CNS for coding purposes, at least in the rat.

Animals

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

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

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

Mechanism for the bitter tasting potency of peptides using O-aminoacyl sugars as model compounds.

In order to study the role of hydrophobicity in bitter peptides, several O-aminoacyl sugars, in which amino acids or peptides were attached to the 2- and 3-position of methyl alpha-D-glucopyranoside, were synthesized and sensory analyses were carried out. It was found that the bitterness increased as the hydrophobicity of compounds increased, implying that the bitterness receptor recognizes the hydrophobicity of bitter peptides. A structure for the bitterness receptor is also discussed.

Amino Acid Sequence

Transduction mechanisms for the taste of amino acids.

Amino acids are important taste stimuli for a variety of animals. One animal model, the channel catfish, I. punctatus, possesses sensitive taste receptor systems for several amino acids. Neurophysiological and biochemical receptor binding studies suggest the presence of at least three receptor pathways: one is a relatively nonspecific site(s) responsive to short-chain neutral amino acids such as L-alanine (L-ALA); another is responsive to the basic amino acid L-arginine (L-ARG); still another is a low affinity site for L-proline (L-PRO). Several possible transduction pathways are available in the taste system of this animal model for these amino acids. One of these, formation of inositol trisphosphate (IP3) and cyclic AMP (cAMP), is mediated by GTP-binding regulatory proteins, while another involves ion channels directly activated by stimuli. L-ALA is a potent stimulus to cAMP and IP3 accumulation, while L-ARG at low concentrations is without effect. On the other hand, L-ARG and L-PRO, but not L-ALA, are able to activate stimulus-specific and cation-selective channels in taste epithelial membranes reconstituted in phospholipid bilayers at the tips of patch pipettes. Preliminary studies using mouse taste tissue demonstrate that monosodium-L-glutamate (MSG) did not enhance production of IP3 or cAMP. However, in reconstitution experiments using taste epithelium of mouse, conductance changes due to MSG are observed. The specificity of this channel(s) and its uniqueness have yet to be determined.

Amino Acids

Intracellular free calcium concentrations in single taste receptor cells in the guinea pig.

Single, viable taste receptor cells were isolated from the tongue of the guinea pig by enzymatic digestion and mechanical dissociation. The cells could be classified into flask, spindle and intermediate shapes. The intracellular free calcium ion concentrations [(Ca2+)i] of these cells were determined using the Ca2+ sensitive dye fura-2 and digital imaging microscopy. All types of cells produced an irreversible increase in (Ca2+)i upon addition of Ca2+ ionophore ionomycin (1 microM) and denatonium (10 microM). There was no evidence of any increase in (Ca2+)i in the taste receptor cells in nominally Ca2+ free solution, and when stimulated by denatonium (10 microM). When 3 mM CaCl2 was added, the (Ca2+)i remarkably increased. This would suggest that the (Ca2+)i increase in the presence of denatonium mainly depended on calcium influx from the extracellular space. There was no increase in case of high potassium (50 mM and 150 mM) or saccharose (1 mM and 5 mM) stimulation. The hypothesis that the increase in (Ca2+)i controls biochemical mechanisms related to the bitter taste transduction process is worthy of further study.

Animals

A photoactivatable Cre-loxP system for spatiotemporal genetic manipulation in mouse taste buds.

Conventional genetic approaches, including global gene KO and conditional KO strategies such as the Cre-loxP system, have some limitations arising from systemic effects or insufficient temporal resolution. The recently developed photoactivatable Cre (PA-Cre) system may have a potential to improve spatiotemporal control of gene manipulation. In this study, we established and validated the feasibility of the PA-Cre system using taste buds as a model. We generated TRE-PA-Cre:R26-rtTA/tdTomato mice to evaluate blue-light-induced Cre recombinase activity. Through systematic optimization of illumination parameters, we found that a single session of blue-light-illumination resulted in limited recombination efficiency, whereas a multisession illumination strategy markedly increased recombination efficiency. To further assess the utility of the PA-Cre system for gene KO, we generated TRE-PA-Cre:R26-rtTA:Tas1r3-flox mice and targeted a taste-related gene Tas1r3. Genomic DNA quantitative PCR and reverse transcription-quantitative PCR both showed partial reductions in Tas1r3 at the DNA and mRNA levels, respectively. Behavioral assays further revealed a selective decrease in sensitivity to sweet and umami stimuli. Together, these findings demonstrate PA-Cre-mediated gene manipulation in taste buds and establish a practical optical activation paradigm, providing a high-spatiotemporal-resolution tool for investigating gene function in optically targeted regions.

Animals

Salt taste and disease.

Sodium appetite reflects the importance of sodium homeostasis and the relative scarcity of sodium for many terrestrial animals. Man, for various reasons, also seems to have a specific preference for salt which he consumes in excess of need, and this has been characterized as an important contributor to hypertension. Gustatory sensibility is necessary for the development of sodium appetite. Thus, research on the possible role salt taste sensitivity plays in controlling NaCl consumption in the sodium deficient rat was reviewed as a potential model for the study of salt taste and hypertension in man. Taste acuity experiments began first by examining salt taste thresholds. These studies found that thresholds were not altered by sodium deficiency in rat and the results in hypertensive humans were inconclusive. Threshold determinations may not reveal true sensitivity differences because they varied significantly across experiments and because they are restricted to a small portion of the intensity domain. When research was directed to suprathreshold stimuli, concentrations a rat or man might normally experience, the evidence suggested that hypertensive humans, like sodium-deficient rats, were less sensitive to the taste of salt. This reduced sensitivity may account, in part, for the fact that these two groups consume more salt.

Adrenal Glands

Evaluation of sensory irritation from acrolein-formaldehyde mixtures.

Groups of mice were exposed to eleven combinations of acrolein-formaldehyde atmospheres and their respiratory rate was monitored. A mathematical model, previously derived for analysis of taste receptor stimulation, was applied to the data obtained for each of the above chemicals alone and in combination. The results obtained suggest that such a model adequately described sensory irritation due to these chemicals and indicates that competitive agonism exists between acrolein and formaldehyde when present together.

Acrolein