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Transmembranous signal transduction through G proteins : Implication for the pathophysiology of mental disorders

Research Project

Project/Area Number 09670970
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

ODAGAKI Yuji  Hokkaido Univ.Grad.School of Med., Assist.Prof., 医学部・附属病院, 講師 (10221160)

Co-Investigator(Kenkyū-buntansha) KUSUMI Ichiro  Hokkaido Univ.Grad.School of Med., Assist.Prof., 医学部・附属病院, 講師 (30250426)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsG-protein / GTPase / Receptor / cyclic AMP / CREB / Mastoparan / neuropeptide Y / Depression
Research Abstract

The assay method for agonist-induced stimulation of high-affinity GTPase activity was developed and applied to membranes prepared from rat brain, postmortem human brain, and human blood platelets to investigate the functional interaction between some receptors and their coupled G proteins. This method was shown to be suitable for detection of the functional activation of the G proteins that are negatively coupled to adenylyl cyclase, i.e.G_i family. Indeed, it has been shown that glutamate-stimulated high-affintiy GTPase activity in rat cerebral cortical, striatal, and hippocampal membranes is mediated through group II metabotropic glutamate receptors, which are known to inhibit adenylyl cyclase activity when stimulated. Furthermore, it has been shown that activation of G proteins coupled with some receptors negatively coupled to adenylyl cyclase, especially GABA_B receptors, can be detected in frontal cortical membranes prepared from postmortem human brains. This method was also utilized to investigate the functional activation of G proteins by some peptides, e.g.wasp venom mastoparan and neuropeptide Y, which is not mediated specific receptors but takes place directly or receptor-independently. We also tried to identify the G protein subtypes involved in receptor-mediated high-affinity GTPase activity, and found that G_<i2> was involved in the GABA_B receptor-mediated response in rat cortical membranes. The stimulatory effects of epinephrine and thrombin on high-affinity GTPase activity in human platelet membranes were not significantly different between affective disorder patients and control subjects. On the other hand, cyclic AMP response element binding protein (CREB) levels determined with western blotting in postmortem frontal cortex were upregulated in depressed suicide victims compared with control subjects. This assay provides useful information about mechanisms of functional activation of G proteins, in particular G_i, even in native membranes.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Yuji Odagaki: "Effects of the wasp venom peptide, wastoparan, on GTP hydrolysis in rat brain membranes"Br.J.Pharmacol.. 121. 1406-1412 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Odagaki: "Lack of interfering effects of lithium on receptor/G protein conpling in human plateler and rat brain membranes"Biol.Psychiat.. 42. 697-703 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 小田垣雄二: "血小板を用いた三量体G蛋白機能の検討"神経精神薬理. 19. 883-888 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Odagaki: "Receptor-mediated and receptor-independent activation of G-proteins in rat brain membranes"Life Sci. 62. 1537-1541 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Odagaki: "Measurement of receptor-mediated functional activation of G proteins in postmortem human brain membranes"Brain Res. 789. 84-91 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Odagaki: "Activation of G proteins by neuropeptide Y and GABA_B receptor agohists in rat cerebral contical membranes through distiuct modes of action."J.Pharmacol.Exp.Ther.. 291. 1250-1256 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Odagaki: "Methods in molecular Biology, vol.83, Receptor Signal Transduction Protocols"Humana Press. 132-141 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yuji Odagaki: "Signal Transduction in Affective Disorders"Springer-Verlag. 97-119 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi and T.Koyama: "Effects of the wasp venom peptide, mastoparan, on GTP hydrolysis in rat brain"Br.J.Pharmacol.. 121. 1406-1412 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi and T.Koyama: "Lack of interfering effects of lithium on receptor/G protein coupling in human"Biol.Psychiat.. 42. 697-703 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki and K.Fuxe: "Agonist-induced high-affinity GTP hydrolysis as an index of receptor-mediated G protein activation in mammalian brain membranes."In : Methods in Molecular Biology, Receptor Signal Transduction Protocols (edited by R.A.J.Challis), Human Press, Totowa. vol.83. 132-141 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi and T.Koyama: "Receptor-mediated and receptor-independent activation of G-proteins in"Life Sci.. 62. 1537-1541 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi and T.Koyama: "Postreceptor signal-transduction systems as potential targets of lithium."In : Signal Transduction in Affective Disorders (edited by H.Ozawa, T.Saito and N.Takahata), Springer-Verlag, Tokyo. 97-119 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi, H.Ozawa, T.Saito, N.Takahata, P.Riederer and T.Koyama: "Measurement of receptor-mediated functional activation of G proteins in postmortem human brain membranes."Brain Res.. 789. 84-91 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi, S.Nakagawa and T.Koyama: "Activation of G proteins by neuropeptide Y and GABA_B receptor agonists in rat cerebral cortical membranes through distinct modes of action."J.Pharmacol.Exp.Ther.. 291. 1250-1256 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Nishi, Y.Odagaki and T.Koyama: "Pharmacological characterization of metabotropic glutamate receptor-mediated high-affinity GTPase activity in rat cerebral cortical membranes.Y.Odagaki"Br.J.Pharmacol.. 130. 1664-1670 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Nishi and T.Koyama: "Functional coupling of GABA_B receptors with G proteins that are sensitive to N-ethylmaleimide, suramin, and benzalkonium chloride in rat cerebral cortical membranes."J.Neural Transm.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Odagaki, N.Nishi and T.Koyama: "Stimulation of high-affinity GTPase activity through group II metabotropic glutamate receptors in rat hippocampal and striatal membranes."Japan.J.Pharmacol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nobuyuki Nishi: "Pharmacological characterization of me tabotropic glutamate receptor-medcated high- affinity GTPase activity in rat cerebral cortical membranes"Br.J.Pharmacol. 130. 1664-1670 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuji Odagaki: "Functional coupling of GABAB receptors with G proteins that are Sensitive to N-ethylmaleimide, suraming and benzal konium chloride in rat arebra cortical membran"J.Nenral Transm. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuji Odagaki: "Stimulation of high-aflinity GTPase activity throngh groupII metabotropic glutamate receptor in rat hippocampal and striatal membran"Japan.J.Pharmacol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yuji Odagaki: "Activation of G proteins by neuropeptide Y and γ-aminobutyric acid B receptor agonists in rat cerebral cortical membranes through distinct modes of action"J.Pharmacol.Exp.Ther.. 291. 1250-1256 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuji Odagaki: "Measurement of receptor-mediated functional activation of G proteins in postmortem human brain membrahes" Brain Research. 789. 84-91 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuji Odagaki: "Receptor-mediated and receptor-independent activation of G-proteins in rat brain membranes" Life Sciences. 62. 1537-1541 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yuji Odagaki: "Measurement of receptor-mediated functional activation of G proteins in postmortem human brain membranes" Brain Research. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuji Odagaki: "Receptor-mediated and receptor-independent activation of G-proteins in rat brain membranes" Life Sciences. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuji Odagaki: "Effects of the wasp venom peptide,mastoparan,on GTP hydrolysis in rat brain membranes" British Journal of Pharmacology. 121. 1406-1412 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuji Odagaki: "Lack of interferring effects of lithium on receptor/G protein coupling in human platelet and rat brain membranes" Biological Psychiatry. 42. 697-703 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小田垣雄二: "血小板を用いた三量体G蛋白機能の検討" 神経精神薬理. 19. 883-888 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuji Odagaki: "Methods in Molecular Biology,vol.83,Receptor Signal Transduction Protocols (edited by R.A.J.Challis)" Humana Press, 132-141 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yuji Odagaki: "Signal Transduction in Affective Disorders (edited by H.Ozawa,T.Saito and N.Takahata)" Springer-Verlag, 97-119 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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