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Study on the possibility for drug utilization of peptidergic neurotransmitter using knockout mouse

Research Project

Project/Area Number 07557157
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biological pharmacy
Research InstitutionOsaka University

Principal Investigator

BABA Akemichi  Osaka University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70107100)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Hitoshi  Osaka University, Faculty of Pharmaceutical Sciences, Assistant Researcher, 薬学部, 助手 (30240849)
MATSUDA Toshio  Osaka University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00107103)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1995: ¥8,400,000 (Direct Cost: ¥8,400,000)
KeywordsVIP / PACAP / Receptor / Knockout mouse / Gane targeting / Neurotransmitter / peptide / マウス / 幹細胞
Research Abstract

PACAP has an amino acid sequence identity of 68% with vasoactive intestinal polypeptide (VIP) and regulates a wide range of physiological functions in the central and peripheral nervous systems. Three genes encoding PACAP/VIP receptor subtypes, which bind PACAP with a high affinity, have been cloned, but the physiological significance of each subtype has not been completely characterized. To elucidate the role of the PACAP signaling system, we have used gene targeting in embryonic stem cells to disrupt exon 2 of the PACAP receptor gene, and characterized the mutant mice as well as wildtype mice.
1. The mutant mice had reduced [^<125>I]PACAP-27 binding and cAMP production in their brains.
2. The mutant mice, however, were viable and fertile, and morphologically, histologically and electrophysiologically indistinguishable from their wild-type counterparts.
3. Coexpression of PACAP receptor and PACAP was seen in the sympathetic nervous system of the wild-type mice and rats.
4. In the sympathetic neurons, PACAP stimulates the expression of PACAP receptor and PACAP mRNAs at a transcriptional level.
5. The mechanism of the PACAP production was studied in mouse insulinoma cells.
In conclusion, these results suggest that PACAP acts as a autocrine or paracrine regulatory factor and contributes to sustained activation of the sympathoadrenal system, and that PACAP regulates glucose-stimulated insulin secretion from beta cells by an autocrine mechanism. However, the intact PACAP receptor is not a prerequisite for normal mouse development of for survival.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kyohei Yamamoto: "cloning and characterization of the mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene" Gene. (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Nogi: "Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor mRNA in the rat adrenal gland : localization by in situ hybridization and identification of splice variants" Jpn.J.Pharmacol.75. 203-207 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide receptor chimeras reveal domains that determine specificity of VIP binding and activation" Mol.Pharmacol.52. 128-135 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Nogi: "Distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP),PACAP receptor,vasoactive intestinal polypeptide (VIP),and VIP receptors in the rat superior cervical ganglion" Neurosci.Lett.227. 37-40 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 橋本 均: "Pituitary adenylate cyclase-activating polypeptide(PACAP)受容体の構造および機能" ビタミン. 71. 285-296 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain : An in situ hybridization study." J.Comp.Neurol.371. 567-577 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "cDNA cloning of a mouse pituitary adenylate cyclase-activating polypeptide receptor." Biochim.Biophys.Acta. 1281. 129-133 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain : an in situ hybridization study" J.Comp.Neurol.371. 567-577 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "cDNA cloning of a mouse pituitary adenylate cyclase-activating polypeptide receptor" Biochim.Biophys.Acta. 1281. 129-133 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide receptor chimeras reveal domains that determine specificity of VIP binding and activation" Mol.Pharmacol.52. 128-135 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Nogi: "Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor mRNA in the rat adrenal gland : localization by in situ hybridization and identification of splice variants" Jpn.J.Pharmacol.75. 203-207 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Nogi: "Distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP receptor, vasoactive intestinal polypeptide (VIP), and VIP receptors in the rat superior cervical ganglion" Neurosci.Lett.227. 37-40 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hitoshi Hashimoto: "Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Receptor : Structure and Functional Characterization" Vitamins (Japan). 71. 285-296 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kyohei Yamamoto: "Cloning and characterization of the mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene" Gene. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kyohei Yamamoto: "Cloning and characterization of the mouse pituitary adenylate cyclase-activating polypeptide(PACAP)gene" Gene. 印刷中. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroyuki Nogi: "Pituitary adenylate cyclase-activating polypeptide(PACAP)receptor mRNA in the rat adrenal gland:localization by in situ hybridization and identification of splice variants" Jpn.J.Pharmacol.75. 203-207 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hitoshi Hashimoto: "Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide receptor chimeras reveal domains that determine specificity of VIP binding and activation" Mol.Pharmacol.52. 128-135 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroyuki Nogi: "Distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide(PACAP),PACAP receptor,vasoactive intestinal polypeptide(VIP),and VIP receptors in the rat superior cervical ganglion" Neurosci.Lett.227. 37-40 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 橋本均: "Pituitary adenylate cyclase-activating polypeptide(PACAP)受容体の構造および機能" ビタミン. 71. 285-296 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aino,H.: "Structure of the gene encoding the mouse pituitary adenylate cyclase-activating polypeptide receptor." Gene. 164. 301-304 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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