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1.
PLoS One ; 4(8): e6717, 2009 Aug 21.
Article in English | MEDLINE | ID: mdl-19696921

ABSTRACT

Umami taste (corresponds to savory in English) is elicited by L-glutamate, typically as its Na salt (monosodium glutamate: MSG), and is one of five basic taste qualities that plays a key role in intake of amino acids. A particular property of umami is the synergistic potentiation of glutamate by purine nucleotide monophosphates (IMP, GMP). A heterodimer of a G protein coupled receptor, TAS1R1 and TAS1R3, is proposed to function as its receptor. However, little is known about genetic variation of TAS1R1 and TAS1R3 and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human TAS1R1 and TAS1R3, and the functions of TAS1R1/TAS1R3 variants using a heterologous expression system. Our study demonstrated that the TAS1R1-372T creates a more sensitive umami receptor than -372A, while TAS1R3-757C creates a less sensitive one than -757R for MSG and MSG plus IMP, and showed a strong correlation between the recognition thresholds and in vitro dose-response relationships. These results in human studies support the propositions that a TAS1R1/TAS1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity.


Subject(s)
Taste Perception/genetics , Adult , Amino Acid Substitution , Cell Line , Female , Gene Frequency , Genotype , Haplotypes , Humans , Immunohistochemistry , Male , Polymorphism, Single Nucleotide , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/genetics
2.
Ann N Y Acad Sci ; 1170: 51-4, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19686107

ABSTRACT

Recent molecular studies proposed that the T1r1/T1r3 heterodimer, mGluR1 and mGluR4 might function as umami taste receptors in mice. However, the roles of each of these receptors in umami taste are not yet clear. In this paper, we summarize recent data for T1r3, mGluR1, and mGluR4 as umami taste receptors and discuss receptor systems responsible for umami detection in mice.


Subject(s)
Receptors, G-Protein-Coupled/physiology , Taste/physiology , Animals , Dimerization , Mice , Mice, Knockout , Receptors, G-Protein-Coupled/genetics
3.
Am J Clin Nutr ; 90(3): 747S-752S, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19571210

ABSTRACT

l-Glutamate is known to elicit a unique taste, umami, that is distinct from the tastes of sweet, salty, sour, and bitter. Recent molecular studies have identified several candidate receptors for umami in taste cells, such as the heterodimer T1R1/T1R3 and brain-expressed and taste-expressed type 1 and 4 metabotropic glutamate receptors (brain-mGluR1, brain-mGluR4, taste-mGluR1, and taste-mGluR4). However, the relative contributions of these receptors to umami taste reception remain to be elucidated. We critically discuss data from recent studies in which mouse taste cell, nerve fiber, and behavioral responses to umami stimuli were measured to evaluate whether receptors other than T1R1/T1R3 are involved in umami responses. We particularly emphasized studies of umami responses in T1R3 knockout (KO) mice and studies of potential effects of mGluR antagonists on taste responses. The results of these studies indicate the existence of substantial residual responses to umami compounds in the T1R3-KO model and a significant reduction of umami responsiveness after administration of mGluR antagonists. These findings thus provide evidence of the involvement of mGluRs in addition to T1R1/T1R3 in umami detection in mice and suggest that umami responses, at least in mice, may be mediated by multiple receptors.


Subject(s)
Glutamic Acid , Receptors, G-Protein-Coupled/physiology , Receptors, Metabotropic Glutamate/physiology , Taste Perception/physiology , Taste/physiology , Animals , Chorda Tympani Nerve/physiology , Glossopharyngeal Nerve/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/metabolism , Receptors, Metabotropic Glutamate/metabolism , Signal Transduction/physiology , Taste Buds/metabolism , Taste Buds/physiology
4.
Am J Clin Nutr ; 90(3): 764S-769S, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19625681

ABSTRACT

The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5'-monophosphate and guanosine 5'-monophosphate. There is evidence that a heterodimeric G protein-coupled receptor, which consists of the T1R1 (taste receptor type 1, member 1, Tas1r1) and the T1R3 (taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR(1) (glutamate receptor, metabotropic 1, Grm1) and mGluR(4) (glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species.


Subject(s)
Genetic Variation , Receptors, G-Protein-Coupled/genetics , Receptors, Metabotropic Glutamate/genetics , Taste Perception/genetics , Taste/genetics , Animals , Humans , Mice , Polymorphism, Single Nucleotide , Receptors, G-Protein-Coupled/physiology , Receptors, Metabotropic Glutamate/physiology , Sodium Glutamate , Taste/physiology , Taste Perception/physiology
5.
Diabetes ; 57(10): 2661-5, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18633111

ABSTRACT

OBJECTIVE: It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans. RESEARCH DESIGN AND METHODS: A total of 91 nonobese subjects were used to determine recognition thresholds using a standard stair-case methodology for various taste stimuli. Plasma leptin levels were determined by an enzyme-linked immunosorbent assay at several timepoints during the day under normal and restricted-meal conditions. RESULTS: The recognition thresholds for sweet compounds exhibited a diurnal variation from 0800 to 2200 h that parallels variation for leptin levels, with the lowest thresholds in the morning and the highest thresholds at night. This diurnal variation is sweet-taste selective-it was not observed in thresholds for other taste stimuli (NaCl, citric acid, quinine, and mono-sodium glutamate). The diurnal variation for sweet thresholds in the normal feeding condition (three meals) was independent of meal timing and thereby blood glucose levels. Furthermore, when leptin levels were phase-shifted following imposition of one or two meals per day, the diurnal variation of thresholds for sweet taste shifted in parallel. CONCLUSIONS: This synchronization of diurnal variation in leptin levels and sweet taste recognition thresholds suggests a mechanistic connection between these two variables in humans.


Subject(s)
Circadian Rhythm/physiology , Leptin/blood , Taste Threshold/physiology , Adult , Citric Acid/pharmacology , Female , Humans , Insulin/blood , Male , Quinine/pharmacology , Sodium Chloride/pharmacology , Sodium Glutamate/pharmacology , Taste Buds/drug effects , Taste Buds/physiology , Young Adult
6.
Biochem Biophys Res Commun ; 346(2): 386-92, 2006 Jul 28.
Article in English | MEDLINE | ID: mdl-16765321

ABSTRACT

Gymnema sylvestre (gymnema) contains gurmarin that selectively inhibits responses to sweet substances in rodents. The present study investigated possible interaction between gurmarin and the submandibular saliva in rats fed diet containing gymnema. Electrophoretic analyses demonstrated that relative amounts of two proteins in the saliva clearly increased in rats fed the gymnema diet. However, rats previously given section of the bilateral glossopharyngeal nerve showed no such salivary protein induction. Analyses of amino acid sequence indicate that two proteins are rat kallikrein 2 (rK2) and rat kallikrein 9 (rK9). rK2 and rK9, a family of serine proteases, have a striking resemblance of cleavage site in the protein substrates. Interestingly, gurmarin possesses comparable residues with those rK2 and rK9 prefer. The kallikreins significantly inhibited immunoreaction between gurmarin and antigurmarin antiserum. These results suggest that rK2 and rK9 increased by chemosensory information for the gymnema diet via the glossopharyngeal nerve might cleave gurmarin or at least cause specific binding with it.


Subject(s)
Gymnema/chemistry , Kallikreins/metabolism , Plant Proteins/pharmacology , Saliva/drug effects , Taste/drug effects , Tissue Kallikreins/biosynthesis , Amino Acid Sequence , Animals , Antibodies/immunology , Depression, Chemical , Diet , Enzyme Induction , Glossopharyngeal Nerve/physiology , Male , Plant Proteins/immunology , Rats , Rats, Wistar , Saliva/enzymology
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