1993 Fiscal Year Final Research Report Summary
A search for matabotropic glutamatergic antagonists of biological origins
| Project/Area Number |
03557008
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SUGIYAMA Hiroyuki Kyushu University, Faculty of Science, Professor, 理学部, 教授 (20124224)
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| Co-Investigator(Kenkyū-buntansha) |
MINAKAMI Reiko Kyushu University, Faculty of Science, Assistant Professor, 理学部, 助手 (00239302)
ITO Isao Kyushu University, Faculty of Science, Associate Professor, 理学部, 助教授 (20183741)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Glutamate receptor / Gprotein / Phosphoinositide / Xenopus oocyte |
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| Research Abstract |
Glutamate receptors are classified into two categories, ionotropic and metabotropic glutamate receptors. Here we tried to find biological compounds that may specifically antagonize metabotropic glutamate receptors (mGluRs).
1. We used Xenpus oocytes expressing mGluRs to examine sample materials. First we had to develope a method to remove glutamate which was often contained in the samples at significant concentrations, because it interfered seriously with the assay. We succeeded to develope an efficient method which used a glutamte-specific enzyme, glutamate oxidase.
2. We examined some 20 materials of animal arigins and 30 of plant origins. So far, we could not identify compounds that specifically antagonized mGluRs. However, we could develope a specific agonist : we found that a natural amino acid of a plant origin, 3,5-dihydroxyphenylglycine is a specific agonist for mGluRs coupled to PI metabolism.
3. We found a specific antagonist against serotonergic receptors : we found that a cytokinin plant growth hormone, 6-benzylaminopurine, antagonized the serotonin 5HT_<2C> receptor. This compound was also found to block mGluRs, but much higher concentrations were needed.
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[Publications] Sakimura, K., Kutsuwada, T., Ito, I., Manabe, T., Takayama, C., Kushiya, E., Yagi, T., Aizawa, S., Inoue, Y., Sugiyama, H.and Mishina, M.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit." Naure. 373. 151-155 (1995)
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