The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

Receptor proteins for photoreception have been studied for several decades. More recently, putative receptors for olfaction have been isolated and characterized. In contrast, no receptors for taste have been identified yet by molecular cloning. This report describes experiments aimed at identifying a receptor responsible for the taste of monosodium glutamate (MSG). Using reverse transcriptase (RT)-PCR, we found that several ionotropic glutamate receptors are present in rat lingual tissues. However, these receptors also could be detected in lingual tissue devoid of taste buds. On the other hand, RT-PCR and RNase protection assays indicated that a G-protein-coupled metabotropic glutamate receptor, mGluR4, also is expressed in lingual tissues and is limited only to taste buds. In situ hybridization demonstrated that mGluR4 is detectable in 40–70% of vallate and foliate taste buds but not in surrounding nonsensory epithelium, confirming the localization of this metabotropic receptor to gustatory cells. Expression of mGluR4 in taste buds is higher in preweaning rats compared with adult rats. This may correspond to the known higher sensitivity to the taste of MSG in juvenile rodents. Finally, behavioral studies have indicated that MSG andl-2-amino-4-phosphonobutyrate (l-AP4), a ligand for mGluR4, elicit similar tastes in rats. We conclude that mGluR4 may be a chemosensory receptor responsible, in part, for the taste of MSG.

[1]  J. Desimone,et al.  Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. , 1984, Science.

[2]  B. Lindemann Sweet and Salty: Transduction in Taste , 1995 .

[3]  Takashi Yamamoto,et al.  Electrophysiological and behavioral studies on the taste of umami substances in the rat , 1991, Physiology & Behavior.

[4]  N. Chaudhari,et al.  The Molecular Biology of Glutamate Receptors in Rat Taste Buds , 1994 .

[5]  K. Kurihara,et al.  Identification of novel members of G-protein coupled receptor superfamily expressed in bovine taste tissue. , 1993, Biochemical and biophysical research communications.

[6]  J. Brand,et al.  Transduction mechanisms for the taste of amino acids , 1991, Physiology & Behavior.

[7]  T. Gilbertson The physiology of vertebrate taste reception , 1993, Current Opinion in Neurobiology.

[8]  J B Hurley,et al.  Transduction mechanisms of vertebrate and invertebrate photoreceptors. , 1994, The Journal of biological chemistry.

[9]  A. Robichon,et al.  Gustducin and transducin: a tale of two G proteins. , 2007, Ciba Foundation symposium.

[10]  S. Heinemann,et al.  Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  T. Thomsen,et al.  Galanthamine Hydrobromide in a Long-Term Treatment of Alzheimer's Disease , 1990 .

[12]  D. Tapper,et al.  Taste Stimuli: A Behavioral Categorization , 1968, Science.

[13]  G Vassart,et al.  Selective amplification and cloning of four new members of the G protein-coupled receptor family. , 1989, Science.

[14]  J. Maga Flavor potentiators. , 1983, Critical reviews in food science and nutrition.

[15]  J. Benson,et al.  Expression of mRNA for the N-methyl-d-aspartate (NMDAR1) receptor by the enteric neurons of the rat , 1994, Neuroscience Letters.

[16]  D. Lancet,et al.  Sweet tastants stimulate adenylate cyclase coupled to GTP-binding protein in rat tongue membranes. , 1989, The Biochemical journal.

[17]  R. Norgren,et al.  Preference of old world monkeys for amino acids and other gustatory stimuli: The influence of monosodium glutamate , 1991, Physiology & Behavior.

[18]  William C. Stebbins,et al.  Animal Psychophysics: the design and conduct of sensory experiments , 1970, Springer US.

[19]  H. Grill,et al.  Differences in the taste quality of maltose and sucrose in rats: issues involving the generalization of conditioned taste aversions , 1988 .

[20]  R. Axel,et al.  Alternative splicing generates functionally distinct N-methyl-D-aspartate receptors. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Terri L. Gilbert,et al.  The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins , 1993, Neuron.

[22]  H Nawa,et al.  Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. , 1993, The Journal of biological chemistry.

[23]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[24]  S. Nakanishi,et al.  Sequence and expression of a metabotropic glutamate receptor , 1991, Nature.

[25]  Cori Bargmann,et al.  Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans , 1995, Cell.

[26]  S. Heinemann,et al.  Cloned glutamate receptors. , 1994, Annual review of neuroscience.

[27]  S. Kinnamon,et al.  Sweet taste transduction in hamster taste cells: evidence for the role of cyclic nucleotides. , 1993, Journal of neurophysiology.

[28]  Y. Ninomiya,et al.  Gustatory neural responses in preweanling mice , 1991, Physiology & Behavior.

[29]  Terri L. Gilbert,et al.  Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain. , 1991, Science.

[30]  S. Arai,et al.  Primary structure and cell-type specific expression of a gustatory G protein-coupled receptor related to olfactory receptors. , 1993, The Journal of biological chemistry.

[31]  P. Conn,et al.  Metabotropic glutamate receptors in brain function and pathology. , 1993, Trends in pharmacological sciences.

[32]  S. Nakanishi,et al.  A family of metabotropic glutamate receptors , 1992, Neuron.

[33]  S. Heinemann,et al.  Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins , 1994, Neuron.

[34]  R. Reed,et al.  Signaling pathways in odorant detection , 1992, Neuron.

[35]  Y. Hod,et al.  A simplified ribonuclease protection assay. , 1992, BioTechniques.

[36]  J. Henley,et al.  Kainate-binding proteins: phylogeny, structures and possible functions. , 1994, Trends in pharmacological sciences.

[37]  N. Akaike,et al.  5'-RIBONUCLEOTIDES AS GUSTATORY STIMULI IN RATS ELECTROPHYSIOLOGICAL STUDIES , 1965 .

[38]  R. H. Cagan,et al.  Biochemical studies of taste sensation. IX. Enhancement of L-[3H]glutamate binding to bovine taste papillae by 5'-ribonucleotides. , 1980, Biochimica et biophysica acta.

[39]  R. Axel,et al.  A novel family of genes encoding putative pheromone receptors in mammals , 1995, Cell.

[40]  S. Kinnamon Taste transduction: a diversity of mechanisms , 1988, Trends in Neurosciences.

[41]  D. Melton,et al.  Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. , 1987, Development.

[42]  G. Collingridge,et al.  Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R‐ACPD in rat hippocampal slices , 1993, British journal of pharmacology.

[43]  S. Nakanishi,et al.  Expression of the mRNA for the rat NMDA receptor (NMDAR1) in the sensory and autonomic ganglion neurons , 1992, Neuroscience Letters.

[44]  R. Margolskee,et al.  Gustducin is a taste-cell-specific G protein closely related to the transducins , 1992, Nature.

[45]  A. Faurion Are umami taste receptor sites structurally related to glutamate CNS receptor sites? , 1991, Physiology & Behavior.

[46]  S. Nakanishi,et al.  Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. , 1992, The Journal of biological chemistry.

[47]  Ronald L. Davis Mushroom bodies and drosophila learning , 1993, Neuron.

[48]  S. Nakanishi,et al.  Molecular cloning and characterization of the rat NMDA receptor , 1991, Nature.

[49]  G. Ronnett,et al.  A tale of two senses , 1995, Neuron.

[50]  C. Pfaffmann,et al.  Specificity of acquired aversions to taste qualities in hamsters and rats. , 1980, Journal of comparative and physiological psychology.

[51]  McLaughlin Sk,et al.  33P is preferable to 35S for labeling probes used in In situ hybridization , 1993 .

[52]  James C. Smith Conditioned Suppression as an Animal Psychophysical Technique , 1970 .

[53]  B. Lindemann,et al.  Generation of Cyclic AMP in Taste Buds of the Rat Circumvallate Papilla in Response to Sucrose , 1991 .

[54]  G. Uhl,et al.  Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[55]  B. Lindemann,et al.  Transduction in taste receptor cells requires cAMP-dependent protein kinase , 1988, Nature.

[56]  Masahiko Watanabe,et al.  Distinct gene expression of the N-methyl-d-aspartate receptor channel subunit in peripheral neurons of the mouse sensory ganglia and adrenal gland , 1994, Neuroscience Letters.

[57]  S. Snyder,et al.  Localization of phosphatidylinositol signaling components in rat taste cells: role in bitter taste transduction. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[58]  S. Roper,et al.  The microphysiology of peripheral taste organs , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[59]  G. Westbrook,et al.  Cloning and expression of a new member of the L-2-amino-4-phosphonobutyric acid-sensitive class of metabotropic glutamate receptors. , 1994, Molecular pharmacology.

[60]  K. Torii,et al.  The lateral hypothalamic area as a recognition site for lysine deficiency Effect of inhibin or activin infusion , 1995 .

[61]  T. Gilbertson,et al.  Amiloride reduces the aversiveness of acids in preference tests , 1994, Physiology & Behavior.

[62]  M. Masu,et al.  Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4 , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[63]  M. Akabas,et al.  A bitter substance induces a rise in intracellular calcium in a subpopulation of rat taste cells. , 1988, Science.

[64]  A. Robichon,et al.  Coupling of bitter receptor to phosphodiesterase through transducin in taste receptor cells , 1995, Nature.

[65]  D. Lancet,et al.  Expression of olfactory receptor and transduction genes during rat development. , 1993, Brain research. Developmental brain research.