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A search for matabotropic glutamatergic antagonists of biological origins

Research Project

Project/Area Number 03557008
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurophysiology and muscle physiology
Research InstitutionKYUSHU 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, Associate Professor, 理学部, 助教授 (20183741)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1993: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1992: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1991: ¥5,800,000 (Direct Cost: ¥5,800,000)
KeywordsGlutamate receptor / Gprotein / Phosphoinositide / Xenopus oocyte / イノシトール燐脂質 / glutamate receptor / metabotropic / G protein / グルタミン酸 / 阻害剤 / 生物毒 / 培養細胞
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.

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 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(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasahara,J.: "Inositol phospholipid metabolism in Xenopus oocytes mediated by endogeneous 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." FEBS 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 epsilon 1 subunit." Naure. 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 Science. 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: "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 aniracetam;" 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-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 metabotropic 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-62,a specific inhibitor of calcium/calmodulin-dependent protein kinase II,on long-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.: "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-term potentiation at hippocampal mossy fiber synapses;" NeuroReport. 2. 333-336 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 博之: "神経の可塑性の記憶;「生体における情報伝達」(西塚 泰美・田中 千賀子編集)" 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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