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Vicktoria Danilova

Publications and source records attributed to Vicktoria Danilova.

13 recordsLinked to original sources
PubMed2006

Taste responses to sweet stimuli in alpha-gustducin knockout and wild-type mice.

The importance of alpha-gustducin in sweet taste transduction is based on data obtained with sucrose and the artificial sweetener SC45647. Here we studied the role of alpha-gustducin in sweet taste. We compared the behavioral and electrophysiological responses of alpha-gustducin knockout (KO) and wild-type (WT) mice to 11 different sweeteners, representing carbohydrates, artificial sweeteners, and sweet amino acids. In behavioral experiments, over 48-h preference ratios were measured in two-bottle preference tests. In electrophysiological experiments, integrated responses of chorda tympani (CT) and glossopharyngeal (NG) nerves were recorded. We found that preference ratios of the KO mice were significantly lower than those of WT for acesulfame-K, dulcin, fructose, NC00174, D-phenylalanine, L-proline, D-tryptophan, saccharin, SC45647, sucrose, but not neotame. The nerve responses to all sweeteners, except neotame, were smaller in the KO mice than in the WT mice. The differences between the responses in WT and KO mice were more pronounced in the CT than in the NG. These data indicate that alpha-gustducin participates in the transduction of the sweet taste in general.

Animals↗
PubMed2005

ATP signaling is crucial for communication from taste buds to gustatory nerves.

Taste receptor cells detect chemicals in the oral cavity and transmit this information to taste nerves, but the neurotransmitter(s) have not been identified. We report that adenosine 5'-triphosphate (ATP) is the key neurotransmitter in this system. Genetic elimination of ionotropic purinergic receptors (P2X2 and P2X3) eliminates taste responses in the taste nerves, although the nerves remain responsive to touch, temperature, and menthol. Similarly, P2X-knockout mice show greatly reduced behavioral responses to sweeteners, glutamate, and bitter substances. Finally, stimulation of taste buds in vitro evokes release of ATP. Thus, ATP fulfils the criteria for a neurotransmitter linking taste buds to the nervous system.

Adenosine Triphosphate↗
PubMed2005

Elucidating coding of taste qualities with the taste modifier miraculin in the common marmoset.

To investigate the relationships between the activity in different types of taste fibers and the gustatory behavior in marmosets, we used the taste modifier miraculin, which in humans adds a sweet taste quality to sour stimuli. In behavioral experiments, we measured marmosets' consumption of acids before and after tongue application of miraculin. In electrophysiological experiments responses of single taste fibers in chorda tympani and glossopharyngeal nerves were recorded before and after tongue application of miraculin. We found that after miraculin marmosets consumed acids more readily. Taste nerve recordings showed that after miraculin taste fibers which usually respond only to sweeteners, S fibers, became responsive to acids. These results further support our hypothesis that the activity in S fibers is translated into a hedonically positive behavioral response.

Animals↗
PubMed2005

Probing the sweet determinants of brazzein: wild-type brazzein and a tasteless variant, brazzein-ins(R18a-I18b), exhibit different pH-dependent NMR chemical shifts.

Brazzein is a small, intensely sweet protein. As a probe of the functional properties of its solvent-exposed loop, two residues (Arg-Ile) were inserted between Leu18 and Ala19 of brazzein. Psychophysical testing demonstrated that this mutant is totally tasteless. NMR chemical shift mapping of differences between this mutant and brazzein indicated that residues affected by the insertion are localized to the mutated loop, the region of the single alpha-helix, and around the Cys16-Cys37 disulfide bond. Residues unaffected by this mutation included those near the C-terminus and in the loop connecting the alpha-helix and the second beta-strand. In particular, several residues of brazzein previously shown to be essential for its sweetness (His31, Arg33, Glu41, Arg43, Asp50, and Tyr54) exhibited negligible chemical shift changes. Moreover, the pH dependence of the chemical shifts of His31, Glu41, Asp50, and Tyr54 were unaltered by the insertion. The insertion led to large chemical shift and pKa perturbation of Glu36, a residue shown previously to be important for brazzein's sweetness. These results serve to refine the known sweetness determinants of brazzein and lend further support to the idea that the protein interacts with a sweet-taste receptor through a multi-site interaction mechanism, as has been postulated for brazzein and other sweet proteins (monellin and thaumatin).

Genetic Variation↗
PubMed2004

Sense of taste in a New World monkey, the common marmoset. II. Link between behavior and nerve activity.

In a previous study, we characterized the gustatory system of a New World monkey the common marmoset, Callithrix jacchus jacchus, with electrophysiological techniques by recording from taste fibers of the chorda tympani proper (CT) and glossopharyngeal (NG) nerves. Hierarchical cluster analysis identified three clusters of taste fibers: S fibers, responding predominantly to sweeteners, Q fibers, responding predominantly to bitter stimuli, and H fibers, responding predominantly to acids. In this study, we employed two behavioral techniques, the two-bottle preference (TBP) and conditioned taste aversion (CTA), to study the taste of the compounds used in the previous electrophysiological study. The results showed that compounds that did not stimulate any taste fibers were neither preferred nor rejected. Compounds that activated only S fibers were always preferred over water. When aversion to sucrose was created by the CTA method, these compounds were rejected. Compounds that activated Q fibers were rejected and consumed less than water. We studied the relationship between intake and net response from S and Q fibers in the CT and NG nerves. Intake was measured as a preference ratio in TBP test. The net response was defined as: (S(CT) + S(NG)) - (Q(CT) + Q(NG)), where S(CT) + S(NG) denotes the sum of the responses in S fibers of the CT and NG nerves. Similarly, Q(CT) + Q(NG) represents the sum of the responses in Q fibers of the CT and NG nerves. The relationship between intake and the Net response was linear with a Pearson correlation coefficient 0.85. This study supports our hypothesis that intake is influenced by S and Q fibers, where S fibers serve as a hedonically positive input and Q fibers as a hedonically negative input.

Animals↗
PubMed2004

Behavioral study in the gray mouse lemur (Microcebus murinus) using compounds considered sweet by humans.

This study presents the results from two-bottle preference (TBP) tests performed on the gray mouse lemur (Microcebus murinus), a small Malagasy primate. We found that of 18 compounds considered sweet by humans, M. murinus preferred only six: D-tryptophan, dulcin, fructose, sucrose, SC45647, and xylitol. The animals neither preferred nor rejected acesulfame-K, alitame, aspartame, N-4-cyanophenyl-N'-cyanoguanidineacetate (CCGA), cyanosuosan, cyclamate, monellin, saccharin, suosan, super-aspartame, N-trifluoroacetyl-L-glutamyl-4-aminophenylcarbonitrile (TGC), and thaumatin. Together with previously recorded taste-nerve responses in M. murinus to acesulfame-K, alitame, aspartame, cyclamate, monellin, saccharin, and suosan [Hellekant et al., Chem Senses 18:307-320, 1993b], the current results suggest that these compounds either do not taste sweet to M. murinus or they have an aversive taste component. In this work we also relate these findings to phylogeny.

Animals↗
PubMed2003

Critical regions for the sweetness of brazzein.

Brazzein is a small, heat-stable, intensely sweet protein consisting of 54 amino acid residues. Based on the wild-type brazzein, 25 brazzein mutants have been produced to identify critical regions important for sweetness. To assess their sweetness, psychophysical experiments were carried out with 14 human subjects. First, the results suggest that residues 29-33 and 39-43, plus residue 36 between these stretches, as well as the C-terminus are involved in the sweetness of brazzein. Second, charge plays an important role in the interaction between brazzein and the sweet taste receptor.

Amino Acid Sequence↗
PubMed2003

Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice.

BACKGROUND: Recent progress in discernment of molecular pathways of taste transduction underscores the need for comprehensive phenotypic information for the understanding of the influence of genetic factors in taste. To obtain information that can be used as a base line for assessment of effects of genetic manipulations in mice taste, we have recorded the whole-nerve integrated responses to a wide array of taste stimuli in the chorda tympani (CT) and glossopharyngeal (NG) nerves, the two major taste nerves from the tongue. RESULTS: In C57BL/6J mice the responses in the two nerves were not the same. In general sweeteners gave larger responses in the CT than in the NG, while responses to bitter taste in the NG were larger. Thus the CT responses to cyanosuosan, fructose, NC00174, D-phenylalanline and sucrose at all concentrations were significantly larger than in the NG, whereas for acesulfame-K, L-proline, saccharin and SC45647 the differences were not significant. Among bitter compounds amiloride, atropine, cycloheximide, denatonium benzoate, L-phenylalanine, 6-n-propyl-2-thiouracil (PROP) and tetraethyl ammonium chloride (TEA) gave larger responses in the NG, while the responses to brucine, chloroquine, quinacrine, quinine hydrochloride (QHCl), sparteine and strychnine, known to be very bitter to humans, were not significantly larger in the NG than in the CT. CONCLUSION: These data provide a comprehensive survey and comparison of the taste sensitivity of the normal C57BL/6J mouse against which the effects of manipulations of its gustatory system can be better assessed.

Acids↗
PubMed2003

Monkey electrophysiological and human psychophysical responses to mutants of the sweet protein brazzein: delineating brazzein sweetness.

Responses to brazzein, 25 brazzein mutants and two forms of monellin were studied in two types of experiments: electrophysiological recordings from chorda tympani S fibers of the rhesus monkey, Macaca mulatta, and psychophysical experiments. We found that different mutations at position 29 (changing Asp29 to Ala, Lys or Asn) made the molecule significantly sweeter than brazzein, while mutations at positions 30 or 33 (Lys30Asp or Arg33Ala) removed all sweetness. The same pattern occurred again at the beta-turn region, where Glu41Lys gave the highest sweetness score among the mutants tested, whereas a mutation two residues distant (Arg43Ala) abolished the sweetness. The effects of charge and side chain size were examined at two locations, namely positions 29 and 36. The findings indicate that charge is important for eliciting sweetness, whereas the length of the side-chain plays a lesser role. We also found that the N- and C-termini are important for the sweetness of brazzein. The close correlation (r = 0.78) between the results of the above two methods corroborates our hypothesis that S fibers convey sweet taste in primates.

Animals↗
PubMed2002

Oral sensation of ethanol in a primate model III: responses in the lingual branch of the trigeminal nerve of Macaca mulatta.

Ethanol administered orally has been shown to elicit a powerful response in rhesus monkey taste nerves. In this study we focused on the effects of ethanol on lingual non-gustatory receptors by recording from 70 single lingual nerve fibers. Of these 70 fibers, 54 (78%) responded to one or more concentrations of 0.7-12 M ethanol; 16 fibers (22%) were not affected. In 48 (69%) fibers, ethanol increased nerve activity, whereas 6 fibers (9%) exhibited suppression, which was displayed as a diminished response to mechanical stimulation. The excitatory response was characterized by regular impulse activity after a latency of 3-40 sec. With higher concentrations of ethanol, the latency became shorter, and the impulse activity evoked became higher. In many fibers the response peaked and ceased before the end of the 52-sec long-stimulation period. Most of the fibers affected by ethanol responded to light touch and cooling. During repeated touch, ethanol initially potentiated and then abolished the response to mechanical stimulation. Methanol and propanol gave similar results. Butanol only inhibited nerve activity.

1-Propanol↗
PubMed2002

Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin.

The transduction of responses to bitter and sweet compounds utilizes guanine nucleotide binding proteins (G proteins) and their coupled receptors. Alpha-gustducin, a transducin-like G protein alpha-subunit, and rod alpha-transducin are expressed in taste receptor cells. Alpha-gustducin knockout mice have profoundly diminished behavioral and electrophysiological responses to many bitter and sweet compounds, although these mice retain residual responses to these compounds. Alpha-gustducin and rod alpha-transducin are biochemically indistinguishable in their in vitro interactions with retinal phosphodiesterase, rhodopsin and G protein betagamma-subunits. To determine if alpha-transducin can function in taste receptor cells and to compare the function of alpha-gustducin versus alpha-transducin in taste transduction in vivo, we generated transgenic mice that express alpha-transducin under the control of the alpha-gustducin promoter in the alpha-gustducin null background. Immunohistochemistry showed that the alpha-transducin transgene was expressed in about two-thirds of the alpha-gustducin lineage of taste receptor cells. Two-bottle preference tests showed that transgenic expression of rod alpha-transducin partly rescued responses to denatonium benzoate, sucrose and the artificial sweetener SC45647, but not to quinine sulfate. Gustatory nerve recordings showed a partial rescue by the transgene of the response to sucrose, SC45647 and quinine, but not to denatonium. These results demonstrate that alpha-transducin can function in taste receptor cells and transduce some taste cell responses. Our results also suggest that alpha-transducin and alpha-gustducin may differ, at least in part, in their function in these cells, although this conclusion must be qualified because of the limited fidelity of the transgene expression.

Analgesics, Non-Narcotic↗
PubMed2002

Sense of taste in a new world monkey, the common marmoset: recordings from the chorda tympani and glossopharyngeal nerves.

Whole nerve, as well as single fiber, responses in the chorda tympani proper (CT) and glossopharyngeal (NG) nerves of common marmosets were recorded during taste stimulation with three salts, four acids, six bitter compounds and more than 30 sweeteners. We recorded responses of 49 CT and 41 NG taste fibers. The hierarchical cluster analysis distinguished three major clusters in both CT and NG: S, Q, and H. The S(CT) fibers, 38% of all CT fibers, responded only to sweeteners. The S(CT) fibers did not respond during stimulation with salts, acids, and bitter compounds but exhibited OFF responses after citric and ascorbic acids, quinine hydrochloride (QHCl), and salts (in 80% of S(CT) fibers). S(NG) fibers, 50% of all NG fibers, also responded to sweeteners but not to stimuli of other taste qualities (except for citric acid, which stimulated 70% of the S(NG) fibers). Some sweeteners, including natural (the sweet proteins brazzein, monellin) and artificial [cyclamate, neohesperidin dihydrochalcone (NHDHC), N-3,5-dichlorophenyl-N'-(S)-alpha-methylbenzylguanidineacetate (DMGA), N-4-cyanophenylcarbamoyl-(R,S)-3-amino-3-(3,4-methylenedioxyphenyl) propionic acid (CAMPA)] did not elicit responses in the S fibers. In general, the response profiles of the S(CT) and S(NG) clusters were very similar, the correlation coefficient between the responses to sweeteners in these clusters was 0.94. Both the Q(CT) and the Q(NG) fibers (40 and 46% of all fibers) were predominantly responsive to bitter compounds, although their responses to the same set of bitter compounds were quite different. Sweeteners with sweet/bitter taste for humans also stimulated the Q clusters. The H clusters (22 and 3% of all fibers) were predominantly responsive to acids and did not respond to stimuli of other taste qualities. However, bitter stimuli, mainly QHCl, inhibited activity in 70% of H(CT) fibers. Among a total of 90 fibers from both nerves there was only 1 NaCl-best fiber in CT. We found, however, that 35% of the CT fibers reacted to salts with inhibition of activity during stimulation, followed by an OFF response. This OFF response was diminished or eliminated by amiloride. These characteristics indicate that amiloride-sensitive sodium channels are involved in salt transduction in marmosets. In the two NG fibers responding to NaCl, we recorded neither suppression by amiloride nor OFF responses. Comparison of marmoset data with those of other nonhuman primates studied, rhesus and chimpanzee, demonstrates phylogenetic trends in the organization of taste system. This can help to uncover pathways of primate evolution.

Animals↗