Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Introductory Remarks on Umami Research: Candidate Receptors and Signal Transduction Mechanisms on Umami
1 Section of Fundamental Oral Health Care Science, Faculty of Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan and 2 Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan
Correspondence to be sent to: Yuzo Ninomiya, e-mail: nino{at}dent.kyushu-u.ac.jp
Key words: mammal, MSG, receptor, research history, transduction, umami
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Umami as a unique taste |
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Nearly a century ago, Ikeda insisted that there existed one other taste which is distinct from the four basic tastes of sweet, sour, salty and bitter, and tried to isolate a unique taste substance from a major ingredient of Japanese broth, seaweed Laminaria japonica. He identified glutamic acid as the taste substance and named the taste of glutamate umami. His paper in old-style Japanese was recently translated into English and published in this journal (Ikeda, 2002
). His discovery and assertion, however, had remained unnoticed for
decades because the taste of glutamate is subtle and perceived more clearly at moderate
concentrations than at high concentrations.
Since about 1980, research on umami taste has proceeded on a larger scale. In 1985,
the first international symposium on umami was held in Hawaii, the most basic issue
discussed being whether umami was a unique taste quality. A multidimensional scaling
analysis of similarity judgement among various taste substances in humans showed that
monosodium glutamate (MSG) is located outside the taste tetrahedron (Schiffman and Gill, 1987). The same result was
obtained from the analysis of generalization patterns among chemicals in mice conditioned
to avoid MSG (Ninomiya and Funakoshi,
1987). These results suggested that the taste of MSG cannot be reproduced by
mixing the four basic tastes and is independent of them.
A big breakthrough was made by the recent discovery of a variant of brain-expressed
metabotropic glutamate receptor 4 (mGluR4) with a truncated N-terminal (Chaudhari et al., 2000) and the T1R1
+ T1R3 heterodimer receptor (Li et
al., 2002;
Zhao et al., 2003), which
are expressed in heterologous taste cells and respond to glutamate at taste-effective
concentrations. These findings clearly demonstrated the presence of umami-specific
receptors and strongly supported the idea that umami is a unique taste.
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Tongue regional differences in umami sensitivity |
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TopUmami as a unique...Tongue regional differences in...Recent investigations of...Possible transduction mechanisms...References |
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Tongue regional difference was clearly shown in gustatory neural responses to umami substances. Ninomiya and colleagues (Ninomiya and Funakoshi, 1987
;
Ninomiya et al., 2000)
reported that MSG-best (M-type) fibers were exclusively found in the glossopharyngeal
(GL) nerve innervating the posterior tongue and some of M-type fibers displayed marked
synergism between MSG and guanosine 5'-monophosphate (GMP), which is a typical
nature of umami response. In contrast, in the chorda tympani (CT) nerve innervating the
anterior tongue, amiloride-sensitive NaCl-best fibers exhibited robust responses to MSG,
which may be due to high concentration of Na+ dissociated from MSG. Some
sucrose-best fibers in the CT also responded to MSG and showed the synergism between MSG
and GMP. These phenomena suggest that the umami component of the MSG response in the CT
may be masked by greater salty or sweet components, while that in the GL is more dominant
than salty or sweet components. Thus, for the umami-specific information, the M-type
fibers in the GL nerve may play a crucial role in mice.
Greater sensitivities to umami substances in the posterior than the anterior part of
the tongue were confirmed in primates. The electrophysiological studies in rhesus monkeys
(Hellekant et al., 1997)
revealed the presence of M-type fibers in the GL but not in the CT. The human
psychophysical study (Yamaguchi and Ninomiya,
2000) demonstrated that taste sensitivities to MSG and a mixture of MSG and
inosine 5'-monophosphate (IMP) were much higher at the back than at the front of
the tongue. Thus, most investigators consider that the information from the posterior
tongue is important for umami taste.
Unlike other species, rat GL nerves displayed very poor responses to MSG and IMP
(Sako et al., 2000),
suggesting that umami-specific information may be poor in rats. This feature may relate
to the result that rats could not distinguish MSG from sucrose or NaCl (Yamamoto et al., 1991).
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Recent investigations of candidate umami receptors |
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The first candidate umami receptor, taste-mGluR4 (Chaudhari et al., 2000
), was reported to be
dominantly expressed in taste buds on the posterior tongue. The low binding affinity of
this receptor was consistent with the GL nerve sensitivity to MSG. In contrast,
Toyono et al. (2002, 2003)
found more intense expression of brain-mGluR4 at the apical end of taste buds in all
taste papillae by using immunohistochemistry and subsequently revealed the expression of
brain-mGluR1 in the circumvallate papillae by using in situ hybridization. Their
results imply that the glutamate receptors with much higher sensitivities are also
expressed in taste cells. Furthermore, Gabriel et al. (this symposium) have
shown the expression of a variant of brain-mGluR1 with a short amino-terminal
extracellular domain in circumvallate taste cells.
Another stream of research on candidate umami receptors proceeded independently. In
1999, two novel families of G protein-coupled receptors (GPCRs) expressed in taste
receptor cells were identified (Hoon et
al., 1999), one is T1Rs and the other is T2Rs. Concerning the function
of T1R family,
Nelson et al. (2002) reported
that T1R3 responds to sweet substances in combination with T1R2, while it responds to a
wide range of amino acids including glutamate in combination with T1R1 in mice.
Li et al. (2002) revealed
that human T1R1 + T1R3 heterodimer receptors respond specifically to glutamate,
indicating that they are umami specific receptors.
Kim et al. (2003) and
Kusakabe et al. (this symposium) investigated the regional expression patterns
of T1R family and gustducin in the mouse tongue and found that T1R1 and T1R3 are
coexpressed in a subset of taste cells both in the fungiform and circumvallate papillae,
whereas T1R3 is coexpressed with gustducin only in fungiform taste cells, suggesting that
T1R1 + T1R3 receptor may couple to gustducin in the anterior tongue.
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Possible transduction mechanisms for umami taste |
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TopUmami as a unique...Tongue regional differences in...Recent investigations of...Possible transduction mechanisms...References |
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As described above, five candidate umami receptors and involvement of gustducin in transduction have been proposed. Evidence for involvement of T1R3 and gustducin was provided by the behavioral analyses and neural recordings in gustducin- or T1R3-knockout mice, where their preference and neural responses to umami substances were almost abolished (Ruiz et al., 2003
; Damak et al., this symposium). Collectively, it is suggested
that T1R1 + T1R3 receptor coupled to gustducin in the fungiform papilla may be
essential for preference behavior for MSG.
Biochemical and Ca2+-imaging studies have been conducted to
investigate intracellular signaling pathway for umami taste. MSG, mixtures of MSG and
5'-ribonucleotides, or L-AP4 induced cAMP decrease in circumvallate
taste buds (Chaudhari et al., this symposium). IP3 increase in taste
tissue and [Ca2+]i mobilization in isolated taste
cells (Ninomiya et al., 2000;
Sugimoto et al., 2001) and
in a subset of taste cells in a slice preparation of circumvallate papillae (Chaudhari
et al., this symposium) were generated by umami stimulation, suggesting that the
downstream responses may be mediated by phospholipase C (PLC).
The recent investigation with knockout mice has demonstrated PLC-ß2 and a
transient receptor potential channel, TRPM5, are essential molecules for umami taste as
well as sweet and bitter tastes (Zhang et
al., 2003). Toyono et al. (this symposium) further revealed
coexpression of G
q, PLC-ß2 and PLC-ß4, as downstream molecules for
brain-mGluR1 in circumvallate papillae. Damak et al. (this symposium) also
suggested that TRPM5 mediates much of the preference for MSG, though TRPM5-knockout mice
had residual umami responses. Involvement of TRPM5, however, is not consistent with the
data of patch-clamp analysis, where most cells displayed hyperpolarization in response to
umami stimuli (Kinnamon, et al., this symposium).
In conclusion, to date it has been clarified that there are multiple umami receptors, and glutamate information from anterior tongue is predominantly mediated by T1R1 + T1R3 heterodimer receptors coupled to gustducin and play an important role in preference behavior. However, many issues such as regional expression patterns of other candidate umami receptors, especially in the posterior tongue, and the downstream signaling mechanisms and functional roles of them are left to be elucidated.
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References |
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|
TopUmami as a unique...Tongue regional differences in...Recent investigations of...Possible transduction mechanisms...References |
|---|
Chaudhari, N., Lndin, A.M. and Roper, S.D. (2000) A metabotropic glutamate receptor variant functions as a taste receptor. Nat. Neurosci., 3, 113–119.[CrossRef][Web of Science][Medline]
Hellekant, G., Danilova, V. and Ninomiya, Y. (1997) Primate sense of taste: behavioral and single chorda tympani and glossopharyngeal nerve fiber recordings in the rhesus monkey, Macaca mulatta. J. Neurophysiol., 77, 978–993.
Hoon, M.A., Adler, E., Lindemeier, J., Battey, J.F., Ryba, N.J.P. and Zuker, C.S. (1999) Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell, 96, 541–551.[CrossRef][Web of Science][Medline]
Ikeda, K. (2002) New Seasonings. Chem. Senses, 27, 847–849.
Kim, M.-R., Kusakabe, Y., Miura, H., Shindo, Y., Ninomiya, Y. and Hino, A. (2003) Regional expression patterns of taste receptors and gustducin in the mouse tongue. Biochem. Biophys. Res. Commun., 312, 500–506.[CrossRef][Web of Science][Medline]
Li, X., Staszewski, L., Xu H., Durick, K., Zoller, M. and Adler E. (2002) Human receptors for sweet and umami taste. Proc. Natl Acad. Sci. USA, 99, 4692–4696.
Nelson, G., Chandrashekar, J., Hoon, M.A., Feng, L., Zhao, G., Ryba, N.J.P. and Zuker C.S. (2002) An amino-acid taste receptor. Nature, 416, 199–202.[CrossRef][Medline]
Ninomiya, Y. and Funakoshi, M. (1987) Qualitative discrimination among mami and the four basic taste substances in mice. In Kawamura, Y. and Kare, M.R. (eds), Umami: A Basic Taste. Marcel Dekker, New York, pp. 365–385.
Ninomiya, Y., Nakashima, K., Fukuda, A., Nishino, H., Sugimura, T., Hino, A., Danilova, V. and Hellekant, G. (2000) Responses to umami substances in taste bud cells innervated by the chorda tympani and glossopharyngeal nerves. J. Nutr., 130, 950S–953S.
Ruiz, C.J., Wray, K., Delay, E., Margolskee, R.F. and Kinnamon, S.C. (2003) Behavioral evidence for a role of alfa-gustducin in glutamate taste. Chem. Senses, 28, 573–579.
Sako, N., Harada, S. and Yamamoto, T. (2000) Gustatory information of umami substances in three major taste nerves. Physiol. Behav., 71, 193–198.[CrossRef][Medline]
Schiffman, S.S. and Gill, J.M. (1987) Psychophysical and neurophysiological taste responses to glutamate and purinergic compounds. In Kawamura, Y. and Kare, M.R. (eds), Umami: A Basic Taste. Marcel Dekker, New York, pp. 271–288.
Sugimoto, K., Nakashima, K., Yasumatsu, K., Sasamoto, K. and Ninomiya, Y. (2001) Glutamate transduction mechanism in mouse taste cells. Sensory Neuron, 3, 139–154.
Toyono, T., Seta, Y., Kataoka, S., Harada, H., Morotomi, T., Kawano, S., Shigemoto, R. and Toyoshima, K. (2002) Expression of the metabotropic glutamate receptor, mGluR4a, in the taste hairs of taste buds in rat gustatory papillae. Arch. Histol. Cytol., 65, 91–96.[CrossRef][Web of Science][Medline]
Toyono, T., Seta, Y., Kataoka, S., Kawano, S., Shigemoto, R. and Toyoshima, K. (2003) Expression of metabotropic glutamate receptor group I in rat gustatory papillae. Cell Tissue Res., 313, 29–35.[CrossRef][Web of Science][Medline]
Yamaguchi, S. and Ninomiya, K. (2000) Umami and food palatability. J. Nutr., 130, 921S–926S.
Yamamoto, T., Matsuo, R., Fujimoto. Y., Fukunaga, I., Miyasaka, A. and Imoto, T. (1991) Electrophysiological and behavioral studies on the taste of umami substances in the rat. Physiol. Behav., 49, 919–925.[CrossRef][Medline]
Zhang, Y., Hoon, M.A., Chandrashekar, J., Mueller, K. L., Cook, B., Wu, D., Zuker, C.S. and Ryba, J.P. (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell, 112, 293–301.[CrossRef][Web of Science][Medline]
Zhao, G.Q., Zhang, Y., Hoon, M.A., Chandrashekar, J., Erlenbach, I., Ryba, N.J.P. and Zuker C.S. (2003) The receptors for mammalian sweet and umami taste. Cell, 115, 255–266.[CrossRef][Web of Science][Medline]
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