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Molecular genetical analysis on structure and function of GABA_A and GABA_B receptors

Research Project

Project/Area Number 01480143
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KIRIYAMA Kinya  Kyoto Pref. Univ. of Med., Dept. of Pharmacla. Instructor, 医学部, 教授 (20079734)

Co-Investigator(Kenkyū-buntansha) HIROUCHI Masaaki  Kyoto Pref. Univ. of Med., Dept. of Pharmacol. Instructor, 医科部, 助手 (70181196)
橋本 恒一  京都府立医科大学, 医学部, 助手 (00172867)
田口 淳一  京都府立医科大学, 医学部, 助手 (50188132)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1989: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsGABA_A receptor / GABA_B receptor / Purification / cDNA cloning / Primary structure / Monoclonal antibody / Reconstitution / Functional expression / 糖蛋白 / mRNA / αサブユニット / βサブユニット / クロライドイオンチャネル
Research Abstract

Molecular genetical and molecular pharmacological studies on cerebral GABA_A and GABA_B receptors have been employed and the following results were obtained.
1) The alpha_1-subunits of human brain GABA_A receptor consists of 456 amino acid residues and its sequence is similar to that of bovine brain. 2) The single mRNA (4.6Kb) for GABA_A receptor alpha^<>1-subunit is expressed in human brain. 3) The alpha_1-subunit of GABA_A receptor in the human brain possesses exon-intron organization. 4) The alpha_1-subunit of GABA_A receptor in the human brain consists of four transmembrane domains. 5) The microinjection of mRNA for GABA_A receptor alpha_1-subunit from the human brain induces the expression of functionally relevant GABA_A receptor. 6) The GABA_A receptor alpha_1-subunit in the mouse and rat brains is expressed from two mRNAs (4.1 and-4.6K) by an alternative splicing. 7) The 13, 000 fold purification of GABA_B receptor is achieved by baclofen-affinity column chromatography. 8) The GABA_B receptor is negatively coupled with adenylate cyclas, inositol phosphate turnover and calcium channel via Gi or Go protein and these couplings can be eliminated by solubilization of the receptor. 9) The GABA_B receptor is a glycoprotein having the molecular weight of 80 Kda. 10) The GABA_A receptor can be down-regulated by a prolonged exposure to its agonist and this downregulation is caused by the suppression of the expression of mRNA. 11) Both purified GABA_A and GABA_B receptors can be functionally reconstituted on phospholipid vesicles. 12) Monoclonal antibodies for GABA_A and GABA_B receptors (GA-I : Ige, GB-I : IgM) are obtained by the injection of respective receptor protein to Balb/C mouse and by the subsequent screening of specific clones. 13) The derect actions of various drugs on GABA_A and GABA_B receptors can be analyzed using purified and reconstituted each receptor protein.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] M.Hirouchi: "Nucleotide and deduced amino acid sequences of GABA_A receptor α-subunit from human brain." Neurochemistry International. 15. 33-38 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Ohmori: "Functional coupling of γ-aminobutyric acid_B receptor with calciumion channel and GTP protein and its alteration following solubilization." Journal of Neurochemistry. 14. 80-85 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Nishikawa: "Functional coupling of cerebral γ-aminobutyric acid (GABA)_B receptor with phosphatidyl inositol turnover in the brain." Neurochemistry International. 14. 85-90 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Ohmori: "Negative coupling of γ-aminobutyric acid (GABA)_B receptor with posphatidyl inositol turnover in the brain." Neurochemistry International. 15. 359-363 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J.Taguchi: "Immunohistochemical studies on distribution of GABA_A receptor complex in the rat brain using antibody against purified GABA_A receptor complex." Brain Research. 483. 395-401 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Hirouchi: "Expression of mRNA of GABA_A receptor α_1 -subunit in mouse brain." Neurochemistry International. 19. 375-382 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K.Kuriyama: "GABA_B receptor in Mammalian Function" John Wiley & Son Ltd.London, 415 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K.Kuriyama: "Endocrinology and Metabolism,Vo1.7 Ion Channels and Ion Transport" Springer-Verlag,New York, (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Hirouchi: "Nucleotide and deduced amino acid sequences of GABA_A receptor alpha-subunit from human brain" Neurochemistry International. 15. 33-38 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Ohmori: "Functional coupling of gamma-aminobutyric acid_B receptor with calcium ion channel and GTP protein and its alteration following solubilization" Journal of Neurochemistry. 14. 80-85 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Nishikawa: "Functional coupling of cerebral gamma-aminobutyric acid (GABA)_B receptor with adenylate cyclas system : Effect of phaclofen" Neurochemistry International. 14. 85-90 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Ohmori: "Negative coupling of gamma-aminobutyric acid (GABA)_B receptor with phosphatidyl inositol turnover in the brain" Neurochemistry International. 15. 359-363 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] J. Taguchi: "Immunohistochemical studies on distribution of GABA_A receptor complex in the rat brain using antibody against purified GABA_A receptor complex" Brain Research. 483. 395-401 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M. Hirouchi: "Expression of mRNA of GABA_A receptor alpha_1 receptor alpha_1-subunit in mouse brain" Neurochemistry International. 19. 375-382 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Kuriyama: John Wiley & Son Ltd., London. GABA_B receptor in Mammalian Function, 415 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] K. Kuriyama: Springer-Verlag, New York. Endocrinology and Metabolism, VO1.7, Ion Channel and Ion Transport, (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 栗山 欣弥: "γーアミノ酪酸(GABA)受容体の構造と機能" 第23回日本医学会総会会誌. 1. 251 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Nakayasu: "Monoclonal antibody to GABA binding protein,a possible GABA_B receptor." Biochemical Biophysical Research Communication. 182. 722-726 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hirouchi: "Expression of mRNA for Gsα and Gi2α during development of mouse cerebral cortical neurons in primary culture." Neuroreport. 2. 766-768 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Kuriyama: "Purification and identification of 61 Kilodalton GABA(γーaminobutyric acid)_B receptor from bovine brain." Molecular Neuropharmacology. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hirouchi: "Expression of mRNA of GABA_A receptor α_1ーsubunit in mouse brain." Neurochemistry International. 19. 375-382 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Ueha: "Direct action of ethanol on cerebral GABA_A receptor complex:Analysis using prified and recenstituted GABA_A receptor complex." Neurochemistry International. 19. 319-325 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Kuriyama: "Endicrinology & Metabolism,Vol.7 Ion Channels and Ion Transport" SpringerーVerlag,New York, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Kuriyama: "Drug Receptor Related to Neuroactive Amino Acids" Munksgaard Int.Publ.Copenhagen, (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Mizutani;K.Kuriyama: "Functional alterations in cerebral GABA_B receptor during alcohol dependence." Japanese Journal of Pharmacology. 55. Suppl.1-349p (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Mizutani;Y.Ohmori;K.Kuriyama: "Neurochemical Studies on GABA receptor (XXVIII)purication of cerebral GABA_B receptor by affinity column chromatography and its characterization." Japanese Journal of Pharmacology. 55. Suppl.1-165p (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Kuriyama;M.Hirouchi: "Expression and regulation of cerebral GABA_A receptor." Japanese Journal of Pharmacology. 55. Suppl.1-31p (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 栗山 欣弥,廣内 雅明: "Cl^-チャネルと中枢抑制機能" 代謝. 27. 233-240 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 栗山 欣弥,廣内 雅明: "GABAレセプタ-" ブレインサイエンス. 1. 171-178 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 栗山 欣弥,廣内 雅明: "脳内γーアシノ酪酸(GABA)受容体の構造と機能" 蛋白質・核酸・酵素. 35. 1455-1464 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Kuriyama;Y.Ohmori: "GABA_B receptor in Mammalian Function. (N.G.Bowery et al eds.)" Wiley Publish.Co (New York), 11 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 栗山 欣弥: "脳のレセプタ-と運動(永津俊治他編)" 平凡社(東京), 17 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 栗山欣弥: "GABAレセプタ-" 代謝. 26巻増刊. 208-214 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Hirouchi,R.Kuwano,T.Katagiri,Y.Takahashi,K.Kuriyama: "Neucleotide and deduced amino acid sequences of GABA_A receptor α-subunit from human brain" Neurochemistry International. 15. 33-38 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Ohmori,M.Hirouchi,J.Taguchi,K.Kuriyama: "Functional coupling of GABA_B receptor with calcium ion channel and GTP-binding protein and its alteration following solubilization of GABA_B receptor" Journal of Neurochemistry. 54. 80-85 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Ohmori,K.Kuriyama: "Negative coupling of GABA_B receptor with phosphatidylinositol turnover in the brain" Neurochemistry International. 15. 359-363 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Nishikawa,K.Kuriyama: "Functional coupling of cerebral GABA_B receptor with adenylate cyclase system:Effect of phaclofen" Neurochemistry International. 14. 85-90 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] J.Taguchi,T.Kuriyama,Y.Ohmori,K.Kuriyama: "Immunohistochemical studies on distribution of GABA_A receptor complex in the rat brain using antibody against purified GABA_A receptor" Brain Research. 483. 395-401 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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