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1999 Fiscal Year Final Research Report Summary

Regulation of Mechanisms underlying signal transduction via sigma-1 receptor and activity of Tyrosine Hydroxylase.

Research Project

Project/Area Number 09680781
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Institute of Psychiatry

Principal Investigator

YAMAMOTO Hideko  Tokyo Institute of Psychiatry, Dept. of Psychopharmacol., Research staff., 東京都精神医学総合研究所, 研究員 (60211645)

Co-Investigator(Kenkyū-buntansha) YAMAKUNI Tohru  Mitsubishi Kasei Institute of Life Sciences, Research staff., 生命科学研究所, 研究員
YAMAMOTO Toshifumi  Yokohama City University, Graduate school of Integrated Science, Laboratory of Molecular Recognition, Associate Professor., 総合理工学研究科, 助教授 (10230575)
Project Period (FY) 1997 – 1999
KeywordsTyrosine Hydroxylase / V-1 / NO / sigma-1 receptors / c-jun / dopamine beta-hydroxylase / mutation / primary cultured neuronal cells
Research Abstract

(1). Mechanism underlying signal transduction via intracelluar sigma-1 receptors. Expression cloning of sigma-1 receptor (sR1) in Xenopus oocytes showed a binding ability for NE-100, a ligand of sR1, as observed in native tissues. Site-directed mutagenesis in the putative transmembrane (TN) domain of sR1 did not alter expression levels of mutant sR1. [ィイD13ィエD1H]NE-100 binding was abolished by the double mutation (S99! and LL105-106AA) or by the single mutation (Y103F). Scatchard analysis using [ィイD13ィエD1H](+)pentazocine as a ligand demonstrated that the single mutation (Y103F) resulted in low affinity, however, the double mutation (S99A, LL105-106AA) had no effect. These findings provide evidence that the putative TM domain of sR1 plays a critical role in ligand-binding.
(2). Kinetic Characterization of the nitric oxide (NO) toxicity for PC12 cells: effects of half-life time of NO release. Effects of low concentrations of nitric oxide (NO) on cell viability using NO donors. Exposure of … More undifferentiated PC12 cells to low concentrations of NO donors resulted in cell death in a dose- and time-dependent manner. The NO-induced cell death was characterized as apoptosis-like cell death. Pretreatment with an antioxidant ascorbic acid completely prevented the cell death. These findings suggest that the cell toxicity induced by NO at low concentrations strongly depends upon the duration of expose to NO from NO-donors.
(3). A novel protein containing cdc 10/SWI6 motifs regulates expression of mRNA encoding catecholamine biosynthesizing enzymes. Mechanisms that control expression of catecholaminergic biosynthesizing enzymes in a transmitter phenotype-specific manner, are poorly understood. We provide evidence that overexpression of a novel cdc10SWI6 motif-containing protein, V-1, elicits the coordinate up-regulation of above enzymes in PC12D, and catecholamine levels are increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic protein/protein adapter and be involved in control of the catecholaminergic phenotype expression via an intracellular pathway signaling to the nucleus. Less

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Yamamoto T, et al.: "Kinetic characterization of the nitric oxide(NO)toxicity for PC12 cells ; effect of half-life time of NO release"Eur. J. Pharmacol.. in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto H, et al.: "Amino acid residues in transmembrane domain of the type 1 sigma receptor critical for ligand binding"FEBS Lett.. 445.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamakuni T, et al.: "A novel catecholamine biosynthesis-promoting protein containing cdc10/SWI6 motifs"J. Biol. Chem..

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamada S. et al.: "Localization of 5-HT_<2A> receptor in rat cerebral cortex and olfactory system revealed by immunohistochemistry using two antibodies raised in rabbit and chicken"Molecular Brain Res..

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawai N, et al.: "Effect of methamphetamine and dopamine receptor antagonists on cholecystokininlike immunoreactivity in the rat medial prefrontal cortex"Pharm.Biochem.Behav..

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawai N, et al.: "Functional Characterization of endothelin receptors on cultured brain capillary endothelial cells of the rat"Neurochem. Int..

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamakuni T,et al.: "Adv.Pharmacol."Academic Press,NY.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本秀子,等.: "精神科治療学 シグマ受容体(σ receptors)."星和書店.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto T, et al.: "kinetic characterization of the nitric oxide (NO) toxicity for PC12 cells; effect of half-life time of NO release"Eur. J. Pharmacol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto H, et al.: "Amino acid residues in transmembrane domain of the type 1 sigma receptor critical for ligand binding."FEBS Lett.. 445. 19-22 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamakuni T, et al.: "A novel catecholamine biosynthesis-promoting protein containing cdc10/SWI6 motifs."J. Biol. Chem.. 273. 27051-27054 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamada S, et al.: "Localization of 5-HTィイD22AィエD2 receptor in rat cerebral cortex and olfactory system revealed by immunohistochemistry using two antibodies raised in rabbit and chicken."Mol. Brain Res.. 54. 199-211 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawai N, et al.: "Effect of methamphetamine and dopamine receptor antagonists on cholecystokininlike immunoreactivity in the rat medial prefrontal cortex."Pharm. Biochem. Behav.. 58. 517-523 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawai N, et al.: "Functional Characterization of endothelin receptors on cultured brain capillary endothelial cells of the rat."Neurochem. Int.. 31. 597-605 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamakuni T, et al.: "A new regulatory protein of catecholamine synthesizing-enzyme expression."In: Adv. Pharmacol. Academic Press, NY. 42. 30-2 (1998)

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      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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