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Study of the affinities of allosteric ligands for G protein-coupled receptors by the measurement of cellular signaling

Research Project

Project/Area Number 26460092
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionShowa Women's University (2017)
Juntendo University (2015-2016)
The University of Tokyo (2014)

Principal Investigator

Suga Hinako  昭和女子大学, 生活科学部, 准教授 (50261186)

Research Collaborator Ehlert FJ.  カリフォルニア大学, アーバイン校・医学部, 教授
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsGPCR / Gタンパク質共役受容体 / ムスカリン受容体 / アセチルコリン / リガンドバイアス / アロステリックリガンド / 細胞応答 / リガンド / 薬理学 / 細胞内カルシウム
Outline of Final Research Achievements

I explored a novel method to analyze affinities of allosteric ligands by measuring a response downstream in the signaling pathway, without using radioligands. I measured carbamylcholine (agonist)-induced signaling responses of cells expressing wild type M2 muscarinic receptor or a constitutively active mutant of M2 muscarinic receptor after partial receptor inactivation by atropine (antagonist) using TGFα shedding assay.
I'm analyzing the data and getting estimates of the isomerization constant of the unoccupied receptor, the sensitivity constant of the signaling pathway, and the more empirical parameters of the receptor population including the observed affinities and efficacies of allosteric and orthosteric ligands, including inverse agonists, and the efficacy of the unoccupied receptor (i.e., constitutive activity). My method will provide a more meaningful analysis of structure-activity relationships, and an absolute measure of agonist bias.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 Other

All Int'l Joint Research (3 results) Presentation (2 results) Remarks (2 results)

  • [Int'l Joint Research] カリフォルニア大学アーバイン校(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学アーバイン校(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] カリフォルニア大学アーバイン校(米国)

    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞応答測定によるGタンパク質共役受容体の親和性の解析2017

    • Author(s)
      須賀 比奈子
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] パーキンソン病原因遺伝子産物PINK1の促進剤及び阻害剤の探索と作用機構の解析2016

    • Author(s)
      須賀比奈子、遠藤斗志也
    • Organizer
      平成28年度「ミトコンドリアをハブとする構造機能ネットワークの解明」合同研究報告会
    • Place of Presentation
      山形県山形市
    • Related Report
      2016 Research-status Report
  • [Remarks] 昭和女子大学 教員紹介・研究業績

    • URL

      http://gyouseki.swu.ac.jp/swuhp/KgApp?kyoinId=ymisgbgeggy

    • Related Report
      2017 Annual Research Report
  • [Remarks] エフォート率上昇計画

    • URL

      http://receptorpharm.blogspot.jp

    • Related Report
      2016 Research-status Report 2015 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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