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Cellular and molecular studies on the transmembrane mechanism of neuroimmuno-interaction

Research Project

Project/Area Number 02454483
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHokkaido University

Principal Investigator

NOMURA Yasuyuki  Hokkaido University・Fac. Pharmac. Sci. ・Professor, 薬学部, 教授 (00034041)

Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1990: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsNeuro-immune interaction / Neurotransmitter / Muscarinic receptor / Human T lymphocyte / Interleukin / Xenopus oocyte / Novel IL-2 receptor / Neuroprotective effect / T細胞 / ムスカリン性受容体 / トランスメンブラン機構 / cyclic AMP / 細胞内遊離Ca^<2+> / プロテインキナ-ゼC
Research Abstract

To clarify the regulatory mechanism of neurotransmitter in the immune system and the neuroimmune interaction, we have been investigated the presence of muscarinic acetylcholine (mACh) receptors and the transmembrane control in human T lymphocytes. In Jurkat cells which is a cloned human T lymphocyte, muscarinic agonist oxotremorine-M (Oxo-M) caused a transient rise of intracellular concentration of Ca^<2+> ([Ca^<2+>]_i). In addition, Oxo-M stimulated a formation of inositol-1, 4, 5-trisphosphate (IP_3) but did not affect the cyclic AMP level. Oxo-M-induced [Ca^<2+>]_i rise was not affected by omission of Ca^<2+> in the medium and by pretreatment with pertussis, cholera or botulinus toxin. While, Gpp (NH) p and IP_3 caused [Ca^<2+>]_i in digitonin-permeabilized cells. Scatchard analysis of [ ^3H]QNB binding in Jurkat cells indicated : K_D=14 nM and Bmax=45, 000 sites/cell. In addition, Northern blot analysis showed to be expressed m3 type of mACh receptor mRNA. These results suggest tha … More t M_3-mACh receptors exist in human T lymphocytes and the activation of the receptors causes Ca^<2+> mobilization from intracellular Ca^<2+> stores via bacterial toxin-insensitive GTP-binding proteins (probably Gq-like GTP-binding proteins), phospholipase C (PLC) activation and IP_3 formation. Furthermore, to clarify the physiological function of M_3-mACh receptors in the immune system, we then examined effects of M_3-mACh receptor activation on interleukin-2 (IL-2) production from human peripheral blood T lymphocytes.
In electrophysiological assay system using Xenopus oocytes into which rat brain mRNA were microinjected, we identified novel type of IL-2 receptors. The receptors seem to activate PLC via GTP-binding proteins in the brain. We are now planning the cDNA cloning of the novel IL-2 receptors.
MPP^+, a selective neurotoxin to dopamine (DA) neurons, which causes Parkinsonism-like syndromes, decreased the DA content in PC12 cells, a DA neuron-model. IL-6 inhibited MPP^+-induced decrease in the DA content. IL-6 also enhanced the expression of tyrosine hydroxylase mRNA, suggesting that IL-6 exerts protective effects to neurons in the central nervous system. Less

Report

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

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Y.Tokumitsu: "Stimulation of DNA synthesis in Jurkat cells by synergistic action between adenine and guanine nucleotides." FEBS Letters. 288. 81-85 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T.Kaneda: "Effects of oxotremorine-M on the second-messenger generating system in cloned human T lymphocytes,Jurkat cells." Neurochemical Research. 16. 166 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Kitamura: "Effects of nebracetam (WEB 1881 FU),a novel nootropic,as a M_1-muscarinic agonist." Japanese Journal of Pharmacology. 55. 177-180 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 矢田 武: "ヒト末梢血リンパ球のILー2産生およびDNA合成に対するムスカリン性受容体の促進的関与" 神経化学. 30. 340-341 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 野村 靖幸: "血小板および株化Tリンパ球のヒスタミン受容体応答" 第19回薬物活性シンポジウム講演要旨集. 212-217 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Kitamura: "The regulatory mechanism of 〔Ca^<2+>〕_i by H_1-histamine receptors in Jurkat cells,cloned human T lymphocytes." Japanese Journal of Pharmacology. 58(Suppl.). (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Nomura: "Muscarinic receptor-mediated increase in 〔Ca^<2+>〕_i in T lymphocytes,Jurkat cells.in "New Trends in Autonomic Nervous System Research"" Elsevier Science Publishers B.V.(Amsterdam), 55-57 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 野村 靖幸: "T細胞とACh受容体 in“Clinical Neuroscience"" 中外医学社, 791 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Tokumitsu, Y. Yanagawa & Y. Nomura: "Stimulation of DNA synthesis in Jurkat cells by synergistic action between adenine and guanine nucleotide." FEBS Letters. 288. 81-85 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Kitamura, T. Kaneda & Y. Nomura: "Effects of nebracetam (WEB1881FU), a novel nootropic, as a M_1-muscarinic agonist." Japan. J. Pharmacol.55. 177-180 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Nomura & T. Kaneda: "Muscarinic receptor-mediated increase in [Ca^<2+>]_i in T lymphocytes, Jurkat cells." New Trends in Autonomic Nervous System Research. Elsevier. 55-58 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Kaneda & Y. Nomura: "Effects of oxotremorine-M on the second-messenger generating system in cloned human T lymphocytes, Jurkat cells." Neurochem. Res.16. 166 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Yada, Y. Kitamura & Y. Nomura: "Enhancing effects of muscarinic receptor stimulation on interleukin-2 and DNA synthesis in human peripheral blood lymphocytes." Neurochem. Res.((1992))

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Kitamura, Y. Kitayama & Y. Nomura: "The regulatory mechanism of [Ca^<2+>]_i by H_1-histamine receptors in Jurkat cells, cloned human T lymphocytes." Japan. J. Pharmacol.58 Suppl. ((1992))

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y. Itano, Y. Kitamura & Y. Nomura: "Effects of MPP^+ (1-methyl-4-phenylpyridinium ion) on PC 12 cells." Japan. J. Pharmacol.58 Suppl. ((1992))

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] T. Kaneda, Y. Kitamura & Y. Nomura: "Presence of m3 subtype muscarinic acetylcholine receptors and receptor-mediated increase in cytoplasmic concentration of Ca^<2+> in Jurkat, a human leukemic helper T lymphocyte."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Y.Tokumitsu: "Stimulation of DNA synthesis in Jurkat cells by synergistic action between adenine and guanine nucleotides." FEBS Letters. 288. 81-85 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Kaneda: "Effects of oxotremorineーM on the secondーmessenger generating system in cloned human T lymphocytes,Jurkat cells." Neurochemical Research. 16. 166 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Kitamura: "Effects of nebracetam(WEB 1881 FU),a novel nootropic,as a M_lーmuscarinic agonist。" Japanese Journal of Pharmacology. 55. 177-180 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 矢田 武: "ヒト末梢血リンパ球の1Lー2産生およびDNA合成に対するムスカリン低受容体の距進的関与" 神経化学. 30. 340-341 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 野村 靖幸: "血小板および株化Tリンパ球のヒスタミン受容体応答" 第19回薬物活性シンポジウム講演要旨集. 212-217 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Kitamura: "The regulatory mechanism of[Ca^<2+>]_i by H_lーhistamine receptors in Jurkat cells,cloned human T.lymphocytes." Japanese Journal of Pharmacology. 58(Suppl.). (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Nomura: "Muscarinic receptorーmediated increase in[Ca^<2+>]_i in T lymphocytes,in “New Trends in Autonomic Nervous System Research"" Elsevier Science Publishers B.V.(Amsterdam), 55-57 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 野村 靖幸: "T細胞とACh受容体 in“Clinical Neuroscience"" 中外医学社, 791 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 金田 利夫: "ヒトTリンパ球(Jurkat細胞)のムスカリン性受容体応答" 神経化学. 29. 58-59 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 野村 靖幸: "神経伝達物質に対する免疫細胞の応答" 自律神経.

    • Related Report
      1990 Annual Research Report
  • [Publications] Kaneda,Toshio: "The presence of muscarinic acetylcholine receptors and the receptorーmediated increase in cytoplasmic Ca^<2+> in Jurkat,a human leukemic helper T lymphocytes"

    • Related Report
      1990 Annual Research Report
  • [Publications] 野村 靖幸: "Clinical Neuroscience" 中外医学社, (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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