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Neuroendocrine action of adrenomedullin and PAMP

Research Project

Project/Area Number 09671034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionThe University of Tokyo

Principal Investigator

TAKANO Koji  Branch Hospital, University of Tokyo, School of Medicine,, 医学部・附属病院分院, 助手 (20236243)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsADRENOMEDULLIN / ADRENOCORTICOTROPIN / CATECHOLAMINE / PAMP / PROLACTIN / HYPERTENSION / 神経機能
Research Abstract

The neuroendocrine action and neuronal action of adrenomedullin and PAMP was investigated in human pituitary adenoma cells and rat neuronal cell lines. 1. Adrenomedullin(AM) stimulated prolactin release from human prolactin-secreting pituitary adenoma cells dose-dependently by depolarizing the membrane of these cells through the activation of a nonselective cation current. The activation was mediated through Gs and PKA.It is known that intravenous administration of AM stimulates prolactin secretion in normal human subjects. Our data suggest that the stimulation be due to the direct action of AM on prolactin-secreting cells. This study showed the ionic mechanism of AM action for the first time. 2. PAMP inhibited ACTH secretion from human ACTH-secreting pituitary adenoma cells dose-dependently by hyperpolarizing the membrane of these cells. Under the voltage clamp, PAMP induced an outward current accompanied by an increase of the membrane conductance. The PAMP-induced current showed dist … More inct inward rectification and the reversal potential was close to the equilibrium potential of potassium. When the potassium concentration of the extracellular solution was changed, the reversal potential of the PAMP-induced current shifted according to the calculated equilibrium potential of potassium, indicating that PAMP induced an inwardly rectifying potassium current. The hyperpolarization may inhibit action potentials and thus decrease Ca^<2+> influx through the voltage-gated Ca^<2+> channels. 3. The mechanism of action of PAMP on neuronal cells were investigated in NGF-differentiated PCl2 cells. PAMP induced hyperpolarization through the activation of an inwardly rectifying potassium channel. Microinjection of non-hydrolyzable GDP analogue (GDPbetaS) or pretreatment of the cells with pertussis toxin abolished the activation. These indicate that the activation was mediated through a pertussis toxin-sensitive G protein. The subtype of the G protein involved in the signal transduction was investigated using specific antibody against the carboxyl terminal amino acid sequences of Gialpha proteins, which revealed that it was mediated through Gi3. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Koji Takano et al.: "PAMP hyperpolarizes the membrane by activating an inwardly rectifying K^+ current in differentiated PC12 cells" Circulation Research. vol.84. 445-450 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Takano: "Effect of adrenomedullin and PAMP on ion channels." Abstract of the first international symposium on adrenomedullin and PAMP.vol1. 52 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高野幸路: "アドレノメデュリンによるイオンチャネル制御" Molecular Medicine. vol35. 986-991 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高野幸路: "PAMPの刺激伝達系路" 医学のあゆみ. vol.184. 86-89 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Takano and Toshiro Fujita: "Proadrenomedullin NH_2-terminal 20 peptide hyperpolarizes the membrane by activating an inwardly rectifying K+ current in differentiated PC12 cells." Circulation Research. 84. 445-450 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Takano: "Ion channel regulation by adrenomedullin" Molecular Medicine. 35. 986-991 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Takano: "Signal transduction mechanism of PAMP" Journal of Clinical and Experimental Medicine. 184. 86-89 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Takano: "Effect of adrenomedullin and PAMP on ion channels." Abstract the First International Symposium on adrenomedullin and PAMP.52 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koji Takano et al.: "PAMP hyperpolanzes the membrane by activating an inwardly rectifying K^+ current in differentiated PC12 cells" Circulation Research. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高野幸路: "PAMPの刺激伝達経路" 医学のあゆみ. vol.184NO.1. 86-89 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高野幸路: "アドレノメデュリンによるイオンチャネル制御" Molecular Medicine. vol35 NO.8. 986-991 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koji Takano: "EFFECT OF ADRENOHEDULLIN AND PAMP ON ION CHANNELS" Abstract of the First International Symposium on Adrenomedullin and PAMP. 52 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] KOJI TAKANO: "EFFECT OF ADRENOMEDULLIN AND PAMP ON ION CHANNELS" Abstract of the First International Symposium on Adrenomedullin and PAMP. 52 (1998)

    • Related Report
      1997 Annual Research Report

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

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