1993 Fiscal Year Final Research Report Summary
Properties and physiological functions of glutamate receptors coupled to G proteins.
| Project/Area Number |
03404073
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
分子遺伝学・分子生理学
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| Research Institution | KUSHU 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, Assistant 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 / Long-term potentiation / Central nervous system |
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| Research Abstract |
Glutamate receptors are classified into two categories, ionotropic and metabotropic glutamate receptors. Here we studied various aspects of metabotropic glutamate receptors (mGluRs) and obtained the following results :
1. A specific agonist was developed. We found that 3,5-dihydroxyphenylglycine is a specific agonist for mGluRs coupled to PI metabolism.
2. Intracellular reaction mechanisms of mGluRs were examined. We found that two isoforms of G proteins of the Gq subfamily could interact with mGluRs, one of which could negatively regulate PI metabolism under certain conditions.
3. Possible involvement of mGluRs in the hipopcampal mossy fiber LTP was examined. Pharmacological and fuctional characteristics of the reactions which induce the mossy fiber LTP were found to acosely resemble those of mGluRs which are coupled to PI metabolism, suggesting that the mGluRs may play important roles in the mossy fiber LTP.
4. A cDNA clone encoding human mGluR5 was isloated and analyzed. mGlu R5 mRNA was foun to have a variant which is generated by an alternative splcing. The site of the splicing is equivalent to the site of similar splicing in mGluR1, suggesting that the genomic structures of these two receptor genes may be homologous. The splice variants of mGluR5 were found in the rat, mouse and human, and their expressions were specifically regulated depending on the brain regions and the developmental stages.
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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 epsilon1 subunit." Nature. 373. 151-155 (1995)
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