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Query: UNIPROT:P06889 (Mol)
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The pentaacetate esters of several, but not all, monosaccharides were recently found to stimulate insulin release from rat pancreatic islets. We have now compared the taste of solutions of either these esters or the corresponding unesterified monosaccharides. The sweet taste of the latter monosaccharides (0.22 M) ranged as follows: D-glucose approximately or = D-galactose approximately or = D-mannoheptulose > L-glucose. None of the esters (1.7 mM) displayed a sweet taste. However, the alpha- and beta-anomer of D-glucose pentaacetate, the alpha-anomer of D-mannose pentaacetate and the beta-anomer of L-glucose pentaacetate all displayed a bitter taste, whilst both alpha- and beta-D-galactose pentaacetate yielded doubtful results. Since such a situation is comparable to that characterizing the islet B-cell response to these esters, it is proposed that the intracellular interaction between the esters or their hydrolytic products and a protein involved in the recognition of bitter taste in taste buds may participate in their insulinotropic action.
Biochem Mol Biol Int 1997 Dec
PMID:Bitter taste of monosaccharide pentaacetate esters. 944 31

The two anomers of L-glucose pentaacetate were recently found to stimulate insulin release. The insulinotropic action of these esters cannot be attributed to the catabolism in islet cells of their glucidic or acetic moieties. The present review deals with an alternative hypothesis. It is proposed that L-glucose pentaacetate itself directly interacts with a yet unidentified receptor leading to plasma membrane depolarization, induction of electrical activity and increase in the cytosolic concentration of ionized Ca2+. This process displays analogies with the identification of bitter compounds by taste buds. Thus, beta-L-glucose pentaacetate indeed displays a bitter, but no sweet, taste. Purified islet B-cells contain the alpha-gustducin G-protein involved in the perception of bitter taste by taste buds. The pentaacetate ester of beta-L-glucose decreases 86Rb outflow from prelabelled islets, provokes bioelectrical activity in islet B-cells and may induce oscillations of cytosolic Ca2+ in these insulin-producing cells. The effects of beta-L-glucose pentaacetate upon glucagon and somatostatin secretion by the isolated perfused pancreas are also compatible with the present hypothesis. It is proposed that the L-glucose pentaacetate anomers could be used as novel insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus.
Int J Mol Med 1998 Oct
PMID:The riddle of L-glucose pentaacetate insulinotropic action (review). 985 21

Although several pathways of bitter taste signal transduction have been proposed in taste cells, these mechanisms have not been elucidated in detail. To investigate the diversity of responses to bitter stimuli, we recorded the electrophysiological responses to quinine, denatonium and naringin using whole-cell patch clamp technique in isolated taste cells of C57BL/6J mice. Ten mM quinine induced depolarizing response under the current clamp mode, and inward current response under the voltage-clamp mode (holding potential -80 mV) using both K+ (with pseudo intracellular solution) and Cs+ (K+ was substituted by Cs+ in the pseudo intracellular solution) pipettes. However, when the K+ pipette was used, the membrane conductance was suppressed and activated in succession. On the other hand, the membrane conductance was only activated when the Cs+ pipette was used. Half to one mM denatonium induced depolarizing response under the current clamp mode, and outward current response under the voltage clamp mode with both pipettes. Using these pipettes, the membrane conductance was activated or suppressed in the individual case. Naringin-induced responses were not detected in these measurements. These electrophysiological recordings suggest that multiple transduction mechanisms are involved in bitter taste perception in mouse taste cells.
Cell Mol Biol (Noisy-le-grand) 1999 May
PMID:Patch clamp recording of the responses to three bitter stimuli in mouse taste cells. 1038 88

The diversity and evolution of bitter taste perception in mammals is not well understood. Recent discoveries of bitter taste receptor (T2R) genes provide an opportunity for a genetic approach to this question. We here report the identification of 10 and 30 putative T2R genes from the draft human and mouse genome sequences, respectively, in addition to the 23 and 6 previously known T2R genes from the two species. A phylogenetic analysis of the T2R genes suggests that they can be classified into three main groups, which are designated A, B, and C. Interestingly, while the one-to-one gene orthology between the human and mouse is common to group B and C genes, group A genes show a pattern of species- or lineage-specific duplication. It is possible that group B and C genes are necessary for detecting bitter tastants common to both humans and mice, whereas group A genes are used for species-specific bitter tastants. The analysis also reveals that phylogenetically closely related T2R genes are close in their chromosomal locations, demonstrating tandem gene duplication as the primary source of new T2Rs. For closely related paralogous genes, a rate of nonsynonymous nucleotide substitution significantly higher than the rate of synonymous substitution was observed in the extracellular regions of T2Rs, which are presumably involved in tastant-binding. This suggests the role of positive selection in the diversification of newly duplicated T2R genes. Because many natural poisonous substances are bitter, we conjecture that the mammalian T2R genes are under diversifying selection for the ability to recognize a diverse array of poisons that the organisms may encounter in exploring new habitats and diets.
Mol Biol Evol 2003 May
PMID:Adaptive diversification of bitter taste receptor genes in Mammalian evolution. 1267 30

The recent identification of candidate receptor genes for sweet, umami and bitter taste in mammals has opened a door to elucidate the molecular and neuronal mechanisms of taste. Drosophila provides a suitable system to study the molecular, physiological and behavioral aspects of taste, as sophisticated molecular genetic techniques can be applied. A gene family for putative gustatory receptors has been found in the Drosophila genome. We discuss here current knowledge of the gustatory physiology of Drosophila. Taste cells in insects are primary sensory neurons whereupon each receptor neuron responds to either sugar, salt or water. We found that particular tarsal gustatory sensilla respond to bitter compounds. Electrophysiological studies indicate that gustatory sensilla on the labellum and tarsi are heterogeneous in terms of their taste sensitivity. Determination of the molecular bases for this heterogeneity could lead to an understanding of how the sensory information is processed in the brain and how this in turn is linked to behavior.
Cell Mol Life Sci 2004 Jan
PMID:Molecular neurophysiology of taste in Drosophila. 1470 50

Bitter taste perception is crucial for the survival of organisms because it enables them to avoid the ingestion of potentially harmful substances. Bitter taste receptors are encoded by a gene family that in humans has been shown to contain 25 putatively functional genes and 8 pseudogenes and in mouse 33 putatively functional genes and 3 pseudogenes. Lineage-specific expansions of bitter taste receptors have taken place in both mouse and human, but very little is known about the evolution of these receptors in primates. We report the analysis of the almost complete repertoires of bitter taste receptor genes in human, great apes, and two Old World monkeys. As a group, these genes seem to be under little selective constraint compared with olfactory receptors and other genes in the studied species. However, in contrast to the olfactory receptor gene repertoire, where humans have a higher proportion of pseudogenes than apes, there is no evidence that the rate of loss of bitter taste receptor genes varies among humans and apes.
Mol Biol Evol 2005 Mar
PMID:Evolution of bitter taste receptors in humans and apes. 1549 49

The solution structures of complexes of oxyphenonium bromide (OB) with beta- and gamma-cyclodextrins (beta- and gamma-CDs, respectively) in deuterium oxide have been investigated by 500 MHz proton NMR spectroscopy and molecular mechanics calculations. The chemical shifts induced by complex formation provide the 1:1 binding constants and the chemical shift variations, DeltadeltaOB-CD, with complexation for the protons of OB and the CDs. The observed binding constants are very close to those obtained by other methods and are in the following order: beta-CD > gamma-CD > alpha-CD. Initial structures of the complexes are constructed on the basis of the ROESY spectra and the DeltadeltaOB-CD values and are optimized by molecular mechanics calculations. The intermolecular distances between the protons of OB and CD calculated for these structures are well-correlated with the observed ROESY intensities. The cyclohexyl group of OB penetrates deeply into a beta-CD cavity, and the phenyl group is close to the wide rim of the cavity. The phenyl and cyclohexyl groups of OB are both incorporated into a gamma-CD cavity. Furthermore, these structures of the complexes are consistent with the suppression of bitter taste and basic hydrolysis of OB by CDs and the polarity of binding sites of OB.
Mol Pharm
PMID:Solution structures of 1:1 complexes of oxyphenonium bromide with beta- and gamma-cyclodextrins. 1583 13

The sense of bitter taste plays a critical role in how organisms avoid generally bitter toxic and harmful substances. Previous studies revealed that there were 25 intact bitter taste receptor (T2R) genes in humans and 34 in mice. However, because the recent chicken genome project reported only three T2R genes, it appears that extensive gene expansions occurred in the lineage leading to mammals or extensive gene contractions occurred in the lineage leading to birds. Here, I examined the T2R gene repertoire in placental mammals (dogs, Canis familiaris; and cows, Bos taurus), marsupials (opossums, Monodelphis domestica), amphibians (frogs, Xenopus tropicalis), and fishes (zebrafishes, Danio rerio; and pufferfishes, Takifugu rubripes) to investigate the birth-and-death process of T2R genes throughout vertebrate evolution. I show that (1) the first extensive gene expansions occurred before the divergence of mammals from reptiles/birds but after the divergence of amniotes (reptiles/birds/mammals) from amphibians, (2) subsequent gene expansions continuously took place in the ancestral mammalian lineage and the lineage leading to amphibians, as evidenced by the presence of 15, 18, 26, and 49 intact T2R genes in the dog, cow, opossum, and frog genome, respectively, and (3) contractions of the gene repertoire happened in the lineage leading to chickens. Thus, continuous gene expansions have shaped the T2R repertoire in mammals, but the contractions subsequent to the first round of expansions have made the chicken T2R repertoire narrow. These dramatic changes in the repertoire size might reflect the daily intake of foods from an external environment as a driving force of evolution.
Mol Biol Evol 2006 May
PMID:Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Lineage-specific expansions and contractions of the bitter taste receptor gene repertoire in vertebrates. 1648 89

A vast number of structurally diverse bitter compounds need to be detected by a subfamily of only approximately 25 human bitter receptors. Failure in detecting them might be lethal, since some naturally occurring bitter compounds, such as strychnine, are very toxic. This review presents an overview about the enormous progress in the field of mammalian bitter taste research with special emphasis on humans, if data were available. It summarizes the current knowledge about the anatomical basis for bitter taste perception, intracellular signal transduction, evolution, expression and polymorphisms of hTAS2R genes, and the molecular basis for the recognition of bitter compounds.
Cell Mol Life Sci 2006 Jul
PMID:Bitter taste receptors and human bitter taste perception. 1673 25

Recent identification of taste receptors and their downstream signaling molecules, expressed in taste receptor cells, led to the understanding of taste coding in the periphery. Ion channels appear to mediate detection of salty and sour taste. The sensations of sweet, umami and bitter taste are initiated by the interaction of sapid molecules with the G-protein-coupled receptors T1Rs and T2Rs. Mice lacking either PLCbeta2 or TRPM5 diminish behavioral and nerve responses to sweet, umami and bitter taste stimuli, suggesting that both receptor families converge on a common signaling pathway in the taste receptor cells. Nevertheless, separate populations of taste cells appear to be uniquely tuned to sweet, umami and bitter taste. Since PLCbeta2-deficient mice still respond to sour and salty stimuli, sour and salty taste are perceived independent of bitter, umami and sweet taste. In this review, the recent characterization of the cellular mechanisms underlying taste reception and perception, and of taste coding in the periphery will be discussed.
Cell Mol Life Sci 2006 Sep
PMID:Taste perception and coding in the periphery. 1690 11


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