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Screening of drugs for neurodegenerative disorders using neurotransmitter release machinery expressed in Xenopus oocytes

Research Project

Project/Area Number 05557010
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKobe University

Principal Investigator

SHUNTOH Hisato  Kobe University School of Medicine Associate Professor Faculty of Health Science, 医学部, 助教授 (70206259)

Co-Investigator(Kenkyū-buntansha) SAITO Naoaki  Kobe University, Biosignal Res.Center Dept.Mol.pharmacol.Professor, バイオシグナル研究センター, 教授 (60178499)
KUNO Takayoshi  Kobe University School of Medicine Dept.pharmacol.Professor, 医学部, 教授 (50144564)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsCalcineurin / GABA transporter / Long-term potentiation / FK506 / Adaptin / Lipid kinase / Endocytosis / Neural visinin-like calcium-binding proteins / Ca^<2+>結合蛋白質 / オカダ酸 / カリクリンA / セロトニン遊離 / CA1 / NG108-15細胞 / カルシウム動員 / visinin / NVP-1 / cDNAクローニング / カリクリン-A / 脱燐酸化酵素阻害薬
Research Abstract

1. Complementary DNA clones encoding neural visinin-like calcium-binding proteins (NVP-1, NVP-2 and NVP-3) were isolated from rat brain cDNA library. NVP-1, NVP-2 and NVP-3 mRNAs are most highly expressed in brain and are differentially expressed in various regions of rat brain. Furthermore, alterations in NVP-1 may be involvedin the pathology of Phecyclidine-induced psychosis. 2. The effect of phorbol ester on the Na+-dependent uptake of GABA by rat cortical synaptosomes and Xenopus oocytes expressing GAT1 (neuronal GABA transporter) was examined. Protein kinase C may modulate the GABA uptake into presynaptic terminals through the inhibition of GAT1 activity. 3. The serotonin release from RBL-2H3 cells is subject to tonic, Ca2+-independent, inhibition by protein phosphatase 1.4. In the Schaffer collateral-CA1 pathway in rat hippocampal slices, calyculin A induced a long-lasting potentiation of the extracellularfield potentials with a transient increase in glutamate release. 5. Heat shock transiently suppresses the inositol trisphosphate-mediated intracellular calcium signal transduction system and that HSP72 is involved in the recovery of receptor-stimulated calcium rise in the neuronal cells. 6. By screening the mutagen-treated fission yeast cells, immunosuppressant- and temperature- sensitive (its1-6) mutant strains were isolated. Gene products of its1+ and its3+ were beta-adaptin homolog, which is a subunit of adapter protein AP-2, and Pl (4) P5-kinase homolog, which is required for exocytosis, respectively. These results suggest that calcineurin plays an important role in vesicular recycling. In conclusion, our several results provide important clues about the molecular basis of neurotransmitter release and secretory vesicle recycling or endocytosis.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Shogo Matsuyama: "δ-Aminobutyric acid (GABA) modulates neurotransmission in the sinus node via stimulation of the GABAA A receptor." Am.J.Physiol. 264. H1057-H1061 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuo Kajimoto: "Molecular cloning of two additional menbers of the neural visinin-like Ca^<2+>-binding protein gene family" J.Neurochem. 61. 1091-1096 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Norikazu Sakamoto: "Protein phosphatase inhibitors incluces the release of serotonin in rut bosophilic leukemia cells" Biochim.Biophys.Acta.1221. 291-296 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoya Murakami: "Potassium and calciun channel inrolvement in induction of long-lasting synaptic enhancement by calyculiu A,a protein phosphatase inhihator,in ret hippocampal CAl region" Neurosci.Lett.176. 181-184 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shigenori Katayama: "Effect of heat shcck on intracellular calcium mobilization in Newoblastoma x glioma hybrid cells" J.Neurochem.62. 2292-2299 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ichiro Osawa: "Phoroolester-inducecl inhibition of GABA uptake by syxxipto-semes and by Xenopus oocytes expressing GABA trtnspciter (GATl)." Neurosa.Res.19. 287-293 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuo Kajimoto: "Delayed changes in newral visinin-like calcium-binding protein gene expression caused by phenyclidine administration." J.Neural.Transm.100. 257-262 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hisato Shuntoh: "Genetic anolysis of FK506-hypersensitive mutant of Sehizosaccharomyces pomebe." Jap.J.pharmacol.67(Supp21). 82- (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shigeru Honda: "Immunocytochemical ldcalization of three subtypes of GABA transporter in rat retina." Brain Res.Mol.Brain Res.33. 319-325 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shogo Matsuyama: "GABA modulates neurotransmission in sinus node via stimulation of GABA_Areceptor." Am J Physiol. 264 (4 pt 2). 1057-61 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuo Kajimoto: "Molecular cloning of two additional members of the neural visinin-like Ca^<2+> -binding protein gene family." J Neurochem. 61 (3). 1091-6 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Norikazu Sakamoto: "Protein phosphatase inhibitors induce the release of serotonin from rat basophilic leukemia cells (RBL-2H3)." Biochim Biophys Acta. 1221 (3). 291-6 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoya Murakami: "Potassium and calcium channel involvement in induction of long-lasting synaptic enhancement by calyculin A,a protein phosphatase inhibitor, in rat hippocampal CA1 region." Neurosci Lett. 176 (2). 181-4 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shigenori Katayama: "Effect of heat shock on intracellular calcium mobilization in neuroblastoma x glioma hybrid cells." J Neurochem. 62 (6). 2292-9 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ichiro Osawa: "Phorbol ester-induced inhibition of GABA uptake by synaptosomes and by Xenopus oocytes expressing GABA transporter (GAT1)." Neurosci Res. 19 (3). 287-93 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuo Kajimoto: "Delayd changes in neural visinin-like calcium-binding protein gene expression caused by acute phencyclidine administration." J.Neural Trans.100. 257-262 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hisato Shuntoh: "Genetic analysis of FK506-hypersensitive mutant of Schizosaccharomyces pombe." Jap.J.Pharmacology. 67 (Suppl 1). 82 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shigeru Honda: "Immunocytochemical localization of three subtypes of GABA transporter in rat retina." Brain Res Mol Brain Res. 33. 319-325 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuo Kajimoto: "delayed changes in neural visinin-like calcium-binding protein gene expression caused by phencyclidine administration" J. Neural. Transm.100. 257-262 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hisato Shuntoh: "Genetic analysis of FK506-hypersensitive mutant of Schizo saccharomyces pombe" Jap. J. Pharmacol.67(Suppl 1). 82 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shigeru Honda: "Immunocytochemical localization of three subtypes of GABA transporter in rat retina" Brain Res. Mol. Brain Res.33. 319-325 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Norikazu Sakamoto: "Protein Phosphatase inhibitors induce the release of serotonin from rat basophilic leukemia cells(RBL-2H3)" Biochim.Biophys.Acta.1221. 291-296 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Naoya Murakami: "Potassium and calcium channel imvolvement in induction of long-lasting synaptic enhancement by calyculin A,a protein phosphatane inhibitor,in rat hippocompal CA1 region" Neutosci.Lett.176. 181-184 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shigenori Katayama: "Effect of heat shock on intracellular calcium mobilization in Neuroblastoma x glioma hybrid cells" J.Neurochem.62. 2292-2299 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shogo Matsuyama: "γ-Aminobutyric acid(GABA)modulates neurotransmission in the sinus node via stimulation of the GABA_A receptor." Am.J.Physiol.264. H1057-1061 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yasuo Kajimoto: "Molecular cloning of two additonal members of the neural visinin-like Ca^<2+>-binding protein gene family" J.Neurochem.61. 1091-1096 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Norikazu Sakamoto: "Protein phosphatase inhibitors induces the release of serotonin in rat basophilic leukemia cells." Biochim.Biophys.Acta.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shigenori Katayama: "Effect of heat shock on intracellular calcium mobilization in neuroblastoma x glioma hybrid cells." J.Neurochem.(in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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