Functional interaction between TAS2R receptors and G-protein alpha subunits expressed in taste receptor cells.
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Dose-Response Relationship, Drug↗
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Results for “Taste modeling”
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Synthesis, taste properties, and conformational analysis of four stereoisomeric cyclopropane analogs of aspartame.
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Aspartame↗
Electrophysiological responses to bitter stimuli in primate cortex.
Studies investigating fine details of gustatory coding in the domain of each basic taste quality have been completed for sweet, salt, and sour stimuli. In the present experiment, we used chemicals that humans describe as predominantly bitter. We recorded the activity of 50 taste neurons in insular cortex of two cynomolgus macaques. Stimuli were water, fruit juice, glucose, NaCl, HCl, and 16 bitter solutions. In a multidimensional taste space the 16 bitter stimuli formed a coherent cluster composed of three main subgroups: (1) QHCl, phenylalanine, theophylline, caffeine, propyl-thiouracil (PROP), and phenylthiocarbamide (PTC), all of which humans describe as rather purely bitter, (2) MgCl2, CaCl2, NH4Cl, and arginine, which humans describe as salty-bitter, and (3) urea, cysteine, and vitamin B1, which are described as sour-bitter. Vitamin B2, histidine and nicotine were in the center of the bitter cluster. Human descriptions of taste qualities conformed well to the presumed quality of each stimulus as inferred from its position in the multidimensional space (MDS), reinforcing the use of the macaque as a neural model for human gustation.
Animals↗
Mechanism of allosteric regulation of the rod cGMP phosphodiesterase activity by the helical domain of transducin alpha subunit.
The G protein alpha subunit (Galpha) is composed of two distinct folding domains: a GTP-binding Ras-like domain and an alpha helical domain (HD). We have recently reported that the helical domain (HDt) of the vertebrate visual transducin alpha subunit (Galphat) synergizes activation of retinal cyclic GMP phosphodiesterase (PDE) by activated Galphat (Liu, W., and Northup, J. K., (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 12878-12883). Here, we examine the molecular basis for this HD-based signaling regulation, and we provide a new model for the activation of the target effector. The HD proteins derived from visual transducin or taste gustducin alpha subunits, but no other Galpha HD proteins, each attenuate the PDE catalytic core (Palphabeta) and synergize Galphat stimulation of the holoPDE (Palphabetagamma2) with similar apparent affinities. The data from studies of both HDt-mediated attenuation and stimulation indicate that the HDt and the PDE inhibitory subunit (Pgamma) interact with PDE at independent sites and that Palphabeta contains the binding sites for HD. The saturation of both processes by HDt displays positive cooperativity with Hill coefficients of 1.5 for the attenuation of Palphabeta activity and 2.1 for synergism of holoPDE activation. Our data suggest the that Galphat-HDt regulates PDE by allosterically decreasing the affinity of Palphabeta for Pgamma and thus simultaneously facilitating the interaction of the activated Galphat-Ras-like domain with Pgamma. Thus, we propose a new model for the high efficiency of PDE activation as well as deactivation, and, overall, a novel mechanism for controlling fidelity, sensitivity, and efficacy of G protein signaling.
3',5'-Cyclic-GMP Phosphodiesterases↗
Sweet tooth reconsidered: taste responsiveness in human obesity.
Taste responses of normal-weight, obese, and formerly obese individuals for sucrose and fat containing stimuli were examined using a mathematical modelling technique known as the Response Surface Method. The subjects accurately rated intensities of sweetness, fatness, and creaminess of 20 different mixtures of milk, cream, and sugar, and no mixture phenomena or inter-group differences were observed. In contrast, hedonic taste responses varied across subject groups, and were affected differentially by the sucrose and lipid content of the stimuli. Normal-weight subjects optimally preferred stimuli containing 20% lipid and less than 10% sucrose. Obese subjects preferred high-fat stimuli (greater than 34% lipid) that contained less than 5% sucrose, while formerly obese subjects showed enhanced responsiveness to both sugar and fat. Hedonic responsiveness as measured by the optimal sugar/fat ratio was negatively correlated with the degree of overweight (body mass index: weight/height). We hypothesize that sensory preferences for dietary sugars and fats aren determined by body-weight status and may affect the patterns of food consumption.
Adult↗
The effect of VMH lesions, lateral cuts and anterior cuts of food intake, activity level, food motivation, and reactivity to taste.
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Animals↗
The physiology of vertebrate taste reception.
The study of vertebrate taste-cell physiology has advanced dramatically with the use of modern electrophysiological techniques. Recent studies show that taste cells have a wide variety of ion channels which transduce chemical stimuli and are critical to cellular function. Hormones and neurotransmitters modulate ion channel function and, in turn, may affect the performance of the gustatory system.
Animals↗
Main polyphenols in the bitter taste of virgin olive oil. Structural confirmation by on-line high-performance liquid chromatography electrospray ionization mass spectrometry.
Twenty virgin olive oils of extra quality and different bitter intensity were submitted to sensory evaluation and to the determination of polyphenols. A linear regression analysis was carried out assuming, as an independent variable, bitter intensity perceived by tasters, as an independent variable, the concentration (mmol/kg) of dialdehydic and aldehydic forms oleuropein aglycon, and dialdehydic and aldehydic forms ligstroside aglycon. Structural confirmation of these compounds was done by online high-performance liquid chromatography-electrospray ionization-collison-induced dissociation-mass spectrometry. The results obtained demonstrate the essential role played by this compound in the bitter taste of virgin olive oil.
Chromatography, High Pressure Liquid↗
Taste aversion learning: a contemporary perspective.
Food aversion learning has attracted widespread interest because it is a highly adaptive, powerful type of learning with both practical and theoretical ramifications. It has features that make it unusual and robust when compared with other learning paradigms. It has relevance to human problems in that it is likely to contribute to food choice and appetite problems in certain clinical situations. And the robustness of this learning makes it a promising model for neurobiologists interested in understanding neural mechanisms of plasticity. This review provides a broad overview of these aspects of taste aversion learning and points to areas where questions remain and additional research is needed.
Animals↗
Cephalic phase, reflex insulin secretion. Neuroanatomical and physiological characterization.
Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that the CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.
Animals↗
Isomerization and degradation kinetics of hop (Humulus lupulus) acids in a model wort-boiling system.
The rate of isomerization of alpha acids to iso-alpha acids (the compounds contributing bitter taste to beer) was determined across a range of temperatures (90-130 degrees C) to characterize the rate at which iso-alpha acids are formed during kettle boiling. Multiple 12 mL stainless steel vessels were utilized to heat samples (alpha acids in a pH 5.2 buffered aqueous solution) at given temperatures, for varying lengths of time. Concentrations of alpha acids and iso-alpha acids were quantified by high-pressure liquid chromatography (HPLC). The isomerization reaction was found to be first order, with reaction rate varying as a function of temperature. Rate constants were experimentally determined to be k1 = (7.9 x 10(11)) e(-11858/T) for the isomerization reaction of alpha acids to iso-alpha acids, and k2 = (4.1 x 10(12)) e(-12994/T) for the subsequent loss of iso-alpha acids to uncharacterized degradation products. Activation energy was experimentally determined to be 98.6 kJ per mole for isomerization, and 108.0 kJ per mole for degradation. Losses of iso-alpha acids to degradation products were pronounced for cases in which boiling was continued beyond two half-lives of alpha-acid concentration.
Acids↗
The application of stereolithography to the fabrication of accurate molecular models.
The process of stereolithography, which automatically fabricates plastic models from designs created in certain computer-aided design programs, has been applied to the production of accurate plastic molecular models. Atomic coordinates obtained from quantum mechanical calculations and from neutron diffraction data were used to locate spheres in the I-DEAS CAD program with radii proportional to the appropriate van der Waals radii. The sterolithography apparatus was used to build the models using a photosensitive liquid resin, resulting in hard plastic models that accurately represent the computed or experimental input structures. Three examples are given to illustrate how the models can be used to interpret experimental structure-activity data for systems of biological importance or host-guest chemistry: (1) Interpretation of kinetic data for the formation of a stable blocking complex between amiloride analogs and the epithelial sodium channel, (2) interpretation of binding and neural activity data for the interaction of certain amino acids and their analogs at the L-alanine taste receptor of the channel catfish, and (3) interpretation of shape selectivity and rate acceleration in cyclodextrin catalysis using models of the neutron diffraction structure of beta-cyclodextrin and of the transition state for the cleavage of phenyl acetate by the secondary hydroxyl oxygen of beta-cyclodextrin.
Acrylates↗
The effect of thalamic lesions on primate taste preference.
Taste preferences and aversions were examined before and after the placement of bilateral, electrophysiologically guided electrolytic lesions of the thalamic taste area in five Old World monkeys. The only consistent changes shown by all lesioned monkeys on the 30-min, single-bottle intake test were a significantly attenuated consumption of 0.003 M quinine hydrochloride and a significantly elevated intake of 0.1 M sodium chloride. These specific taste deficits are contrary to the global hypogeusia predicted on the basis of previous research. A revised definition of the boundaries of the gustatory thalamus is suggested and the merits of the thalamic monkey preparation are compared with those of the decerebrate rat model.
Animals↗
Taste responsiveness, weight loss, and the ponderostat.
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Animals↗
Gustducin and its role in taste.
The mechanisms responsible for taste signal transductions are very complex. A key molecule, alpha-gustducin, a primarily taste-specific G protein alpha-subunit, was discovered in 1992 and was later found to be involved in both bitter and sweet taste transduction. A proposed mechanism for alpha-gustducin involves coupling specific cell-surface receptors with a cyclic nucleotide phosphodiesterase which would open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, and ultimately leading to release of neurotransmitter. Although "knock-out" animals deficient in the alpha-gustducin gene clearly demonstrate that gustducin is an essential molecule for tasting certain bitter and sweet compounds, the precise role of alpha-gustducin in bitter and sweet taste is presently unclear. Indeed, there are several other signaling mechanisms in sweet and bitter taste, apparently unrelated to alpha-gustducin, that increase cyclic AMP or inositol 1,4,5 trisphosphate. Thus, proposed models for alpha-gustducin and those found by other laboratories may be parallel and interdependent.
Animals↗
Gustatory processing is dynamic and distributed.
The process of gustatory coding consists of neural responses that provide information about the quantity and quality of food, its generalized sensation, its hedonic value, and whether it should be swallowed. Many of the models presently used to analyze gustatory signals are static in that they use the average neural firing rate as a measure of activity and are unimodal in the sense they are thought to only involve chemosensory information. We have recently elaborated upon a dynamic model of gustatory coding that involves interactions between neurons in single as well as in spatially separate, gustatory and somatosensory regions. We propose that the specifics of gustatory responses grow not only out of information ascending from taste receptor cells, but also from the cycling of information around a massively interconnected system.
Action Potentials↗
Sensitization of salt appetite is associated with increased "wanting" but not "liking" of a salt reward in the sodium-deplete rat.
To examine the role of incentive sensitization in the potentiation of salt appetite by prior depletions, the authors assessed the motivation to obtain salt ("wanting") and the palatability of salt ("liking") independently in salt-sensitized rats. Breakpoint on a progressive ratio reinforcement schedule was used to measure salt wanting and taste reactivity was used to measure salt liking in rats with and without a history of Na+ depletion. Salt-sensitized rats displayed higher breakpoints relative to controls. However, a history of Na+ depletion was not associated with a greater positive shift in taste reactivity measures. The data suggest that these components of reward are separable in this model and support the general proposition that sensitization may alter wanting but not liking.
Animals↗
Structure-activity maps for visualizing the graph variables arising in drug design.
Structure-activity problems are characterized by the topological and topographical character of the structural information determining the activity. Traditional statistical methodology requires that this predictive information be mapped to a vector space. To circumvent this vexing conversion of structural information to vector form, the edge-deletion metric is defined on the space of chemical graphs that defines the topology of the molecules. This paper proposes structure-activity maps and transformation-effect maps for directly visualizing the structure-activity relationships. The maps are illustrated using the hypotensive activities of clonidine analogs and the sweet taste of Perillartine analogs.
Clonidine↗