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Properties and physiological functions of glutamate receptors coupled to G proteins.

Research Project

Project/Area Number 03404073
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 分子遺伝学・分子生理学
Research InstitutionKUSHU UNIVERSITY

Principal Investigator

SUGIYAMA Hiroyuki  Kyushu University, Faculty of Science, Professor, 理学部, 教授 (20124224)

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)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥27,900,000 (Direct Cost: ¥27,900,000)
Fiscal Year 1993: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1992: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1991: ¥15,000,000 (Direct Cost: ¥15,000,000)
KeywordsGlutamate receptor / Gprotein / Phosphoinositide / Long-term potentiation / Central nervous system / イノシトール燐脂質 / glutamate receptor / metabotropic / G protein / inositol phospholipid / hippocampus / 可塑性 / アンタゴニスト / 培養細胞
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.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Nakamura,K.: "G protein-mediated inhibition of phosphoinositide metabolism evoked by metabotropic glutamatc receptors in frog oocytes." J.Physiol.(Lond.). 474. 35-41 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sugiyama,H.: "Molecular and functional properties of metabotropic glutamate receptors in the brain." Biomed.Res.15. 29-31 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami,R.: "Molecular clonig and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5." Biochem.Biophys.Res.Commun.199. 1136-1143 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasahara,J.: "Inositol phospholipid metabolism in Xenopus oocytes mediated by endogenous Go and Gi proteins." FEBS Lett.355. 41-44 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakimura,K.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami,R.: "The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development" J.Neurochem.(in press.). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 杉山博之(分担執筆): "「生体における情報伝達」" 南江堂, 280 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sugiyama,H. (分担執筆): "Neuroreceptors,Ion Channels and the Brain" Elsevier Science Publishers, 234 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakamura, K., Nukada, T., Haga, T.and Sugiyama, H.: "G protein-mediated inhibition of phosphoinositide metabolism evoked by metabotropic glutamate receptors in frog oocytes." J.Physiol.(Lond.). 474. 35-41 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami, R., Katsuki, F., Yamamoto, T., Nakamura, K.and Sugiyama, H.: "Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5." Biochem. Biophys. Res. Commun.199. 1136-1143 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sugiyama, H.Nakamura, K., Katsuki, F.and Minakami, R.: "Molecular and functional properties of metabotropic glutamate receptors in the brain." Biomed. Res.15, suppl.1. 29-31 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasahara, J.and Sugiyama, H.: "Inositol phospholipid metabolism in Xenopus oocytes mediated by endogenous Go and Gi proteins." FFBS Lett. 355. 41-44 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami, R., Iida, K., Hirakawa, N.and Sugiyama, H.: "The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development" J.Neurochem.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami,R.,Katsuki,F.and Sugiyama,H.: "A variant of metabotropic glutamate receptor subtype 5:an evolutionary conserved insertion with no termination codon" Biochem.Biophys.Res.Commun.194. 622-627 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Araki,T.,Kenimer,J.,Nishimune,A.,Sugiyama,H.,ら: "Identification of the metabotropic glutamate receptor-1 protein in the rat trigeminal ganglion" Brain Research. 627. 341-344 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sugiyama,H.,Nakamura,K.and Nukada,T.: "Mode of interactions between metaborropic glutamate receptors and G proteins in Xenopus ooctye" Annals of NY Academy of Science22GD03:707. 515-518 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakamura,K.,Nukada,T.,Haga,T.& Sugiyama,H.: "G protein-mediated inhibition of phosphoinositide metabolism evoked by metabotropic glutamate receptors in frog oocytes" J.Physiol.(Lond.). 474. 35-41 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 杉山博之: "「生体における情報伝達」(分担執筆)" 南江堂(西塚泰美・田中千賀子 編集), 322 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 伊藤 功,杉山博之: "「レセプター 〓基礎と臨床〓 」(分担執筆)" 朝倉書店(井村裕夫・岡 哲雄・芳賀達也・岸本英爾 編集), 944 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Minakami,E.Hirose,K.Yoshioka,R.Yoshimura,Y.Misumi,Y.Sakaki,M.Tohyama,H.Kiyama & H.Sugiyama: "Postnatal development of mRNA specific for a metabotropic glutamate receptor in the rat brain." Neuroscience Research. 15. 58-63 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] I.Ito,A.Kohda,S.Tanabe,E.Hirose, M.Hayashi, S.Mitsunaga & H.Sugiyama: "Dihydroxyphenylglycine: a potent agonist of metabotropic glutamate receptors." NeuroReport. 3. 1013-1016 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Sugiyama(分担執筆): "Molecular Basis of Neuronal Connectivity(Eds. M.Satake, K.Obata, H.Hatanaka, E.Miyamoto and T.Okuyama)" Kohko-Do, Niigata, Japan, 199 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Sugiyama & I.Ito(分担執筆): "Neuroreceptors, Ion Channels and the Brain(Eds. N.Kawai, T.Nakajima and E.Barnard)" Elsevier, Holland, 227 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ito,I.,Tanabe,S.,Kohda,A.&Sugiyama,H.: "Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetm;" J.Physiol.(Lond.). 424. 533-543 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sugiyama,H.,Ito,I.and Okada,D.: "Roles of metabotropic and ionotropic Glu receptors in the longーterm potentiation of hippocampal mossy fiber synapses" Adv.Exp.Med.Biol.268. 387-394 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanabe,S.,Ito,I.and Sugiyama,H.: "Possible heterogeneity of metabotopic Glu receptors induced in Xenopus oocytes by rat brain mRNA" Neurosci.Res.10. 71-77 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ito,I.,Hidaka,H.and Sugiyama,H.: "Effects of KNー62,a specific inhibitor of calcium/calmodulinーdependent protein kinase II,on longーterm potentiation in the rat hippocampus" Neurosci.Lett.121. 119-121 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sugiyama,H.,Ito,I.and Tanabe,S.(1991): "Possible heterogeneity of Glu receptors linked to inositol phospholipid metabolism" Fidia Research Foundation Symposium Series. 5. 105-108 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ito,I.and Sugiyama,H.: "Roles of Glu receptors in longーterm potentiation at hippocampal mossy fiber synapses;" NeuroReport. 2. 333-336 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 博之(西塚 泰美,田中 千賀子 編集): "神経の可塑性と記憶;「生体における情報伝達」" 南江堂, (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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