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Exploring for new bioactive peptides using our novel assays

Research Project

Project/Area Number 24659394
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Miyazaki

Principal Investigator

KUWASAKO Kenji  宮崎大学, フロンティア科学実験総合センター, 准教授 (20381098)

Co-Investigator(Kenkyū-buntansha) KATO Johji  宮崎大学, フロンティア科学実験総合センター, 教授 (20274780)
KITAMURA Kazuo  宮崎大学, 医学部, 教授 (50204912)
NAGATA Sayaka  宮崎大学, 医学部, 特任助教 (00452920)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords新規生理活性ペプチド / オーファン受容体 / キメラ遺伝子 / 安定発現株 / FACS解析 / FRET解析
Outline of Final Research Achievements

The discovery of unknown bioactive peptides can help to clarify the complexity of the circulatory system. In the past 23 years, we have discovered several potent hypotensive and vasopressor peptides (e.g., adrenomedullin, its related peptides and proangiotensin-12). Furthermore, we have clarified the mechanisms of the signaling, trafficking and pathophysiological roles of the receptor activity-modifying protein (RAMP)-interacting G protein-coupled receptors (GPCRs). In this study, we have attempted to identify novel bioactive peptides that may be able to bind to the human orphan GPCRs in the circulatory system. We uniquely constructed several chimeras in which some regions of target orphan GPCRs were replaced with the corresponding regions of some known GPCRs that can powerfully cause agonist-induced cAMP production and internalization. Unfortunately, we were unable to identify any bioactive peptides for the intended purpose.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (34 results)

All 2015 2014 2013 2012

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Acknowledgement Compliant: 5 results) Presentation (19 results) (of which Invited: 1 results)

  • [Journal Article] Gender-related alterations in plasma adrenomedullin level and its correlation with body weight gain2015

    • Author(s)
      Kawano S, Kawagoe Y, Kuwasako K, Shimamoto S, Igarashi K, Tokashiki M, Kitamura K, Kato J
    • Journal Title

      Endocr Connect

      Volume: 4 Pages: 42-49

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity2015

    • Author(s)
      Murakami M, Yoshikawa T, Nakamura T, Ohba T, Matsuzaki Y, Sawamura D, Kuwasako K, Yanagisawa T, Ono K, Nakaji S, Yanai K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 458 Pages: 584-589

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel2015

    • Author(s)
      Murakami M, Suzuki T, Wu TW, Kuwasako K, Takahashi E, Watanabe H, Murakami AM, Miyoshi I, Yanagisawa T, Sasano H, Ono K, Ohba T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: not determined

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Biological properties of adrenomedullin conjugated with polyethylene glycol2014

    • Author(s)
      Kubo K, Tokashiki M, Kuwasako K, Tamura M, Tsuda S, Kubo S, Yoshizawa-Kumagaye K, Kato J, Kitamura K
    • Journal Title

      Peptides

      Volume: 57 Pages: 118-121

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of propofol on electrocardiogram measures in mice2014

    • Author(s)
      Shintaku T, Ohba T, Niwa H, Kushikata T, Hirota K, Ono K, Matsuzaki Y, Imaizumi T, Kuwasako K, Sawamura D, Murakami M
    • Journal Title

      J Pharmacol Sci

      Volume: 126 Pages: 351-358

    • NAID

      130004704287

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Functions of the extracellular loop and helix 8 of Family B GPCRs2013

    • Author(s)
      Kuwasako K, Hay DL, Nagata S, Murakami N, Kitamura K, Kato J
    • Journal Title

      Curr Protein Pept Sci

      Volume: 14 Pages: 416-428

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The RAMP-interacting Family B G protein-coupled receptors2013

    • Author(s)
      Kuwasako K
    • Journal Title

      Curr Protein Pept Sci

      Volume: 14 Pages: 416-428

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Big angiotensin-25 : A novel glycosylated angiotensin-related peptide isolated from human urine2013

    • Author(s)
      Nagata S, Hatakeyama K, Asami M, Tokashiki M, Hibino H, Nishiuchi Y, Kuwasako K, Kato J, Asada Y, Kitamura K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 441 Issue: 4 Pages: 757-762

    • DOI

      10.1016/j.bbrc.2013.10.124

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gender difference in relationship between body mass index and development of chronic kidney disease2013

    • Author(s)
      Komura H, Nomura I, Kitamura K, Kuwasako K, Kato J
    • Journal Title

      BMC Res Notes

      Volume: 6 Issue: 1 Pages: 463-463

    • DOI

      10.1186/1756-0500-6-463

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The RAMP-interacting Family B G protein-coupled receptors2013

    • Author(s)
      Kuwasako K
    • Journal Title

      Curr Protein & Peptide Sci

      Volume: ?

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functions of the extracellular loop and helix 8 of Family B GPCRs2013

    • Author(s)
      Kuwasako K, Hay DL, Nagata S, Murakami N, Kitamura K, Kato J
    • Journal Title

      Curr Protein & Peptide Sci

      Volume: ?

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of the single transmembrane domain of human receptor activity-modifying protein 3 in adrenomedullin receptor internalization2012

    • Author(s)
      Kuwasako K, Kitamura K, Nagata S, Nozaki N, Kato J
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 420 Issue: 3 Pages: 582-587

    • DOI

      10.1016/j.bbrc.2012.03.037

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of proangiotensin-12 infused continuously over 14days in conscious rats2012

    • Author(s)
      Komatsu Y, Kida N, Nozaki N, Kuwasako K, Nagata S, Kitamura K, Kato J
    • Journal Title

      Eur J Pharmacol

      Volume: 683 Issue: 1-3 Pages: 186-189

    • DOI

      10.1016/j.ejphar.2012.02.037

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The third extracellular loop of the human calcitonin receptor-like receptor is crucial for the activation of adrenomedullin signalling2012

    • Author(s)
      Kuwasako K, Hay DL, Nagata S, Hikosaka T, Kitamura K, Kato J
    • Journal Title

      Br J Pharmacol

      Volume: 166 Issue: 1 Pages: 137-150

    • DOI

      10.1111/j.1476-5381.2011.01803.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma and tissue concentrations of proangiotensin-12 in rats treated with inhibitors of the renin-angiotensin system2012

    • Author(s)
      Nagata S, Kato J, Kuwasako K, Asami M, Kitamura K
    • Journal Title

      Hypertens Res

      Volume: 35 Issue: 2 Pages: 234-238

    • DOI

      10.1038/hr.2011.165

    • NAID

      10030643913

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] G蛋白共役型受容体(GPCR)の重要な細胞内シグナル分子、β-アレスチンの新規作用:1型アドレノメデュリン受容体(AM1受容体)の細胞内移行の負の制御2015

    • Author(s)
      桑迫 健二、北村 和雄、永田 さやか、加藤 丈司
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 一般住民におけるアドレノメデュリンとナトリウム利尿ペプチドの血中レベルと慢性腎臓病の発症2014

    • Author(s)
      加藤丈司、桑迫健二、北村和雄
    • Organizer
      第18回日本心血管内分泌代謝学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-21 – 2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] メタボリックシンドローム発症要因の解析-清武町研究-2014

    • Author(s)
      野崎尚美、桑迫健二、北村和雄、加藤丈司
    • Organizer
      第37回日本高血圧学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-10-17 – 2014-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Novel functions of two G protein-coupled receptor kinases: their marked inhibitory effect on adrenomedullin type 1 receptor signaling2014

    • Author(s)
      Kenji Kuwasako, Kazuo Kitamura, Sayaka Nagata, Johji Kato
    • Organizer
      The Conference on Bioactive Peptides for Cell-Cell Communication 2014
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-09-10 – 2014-09-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Biological properties of adrenomedullin conjugated with polyethylene glycol2014

    • Author(s)
      Keishi Kubo, Mariko Tokashiki, Kenji Kuwasako, Masaji Tamura, Shugo Tsuda, Shigeru Kubo, Kumiko Yoshizawa-Kumagaye, Johji Kato, Kazuo Kitamura
    • Organizer
      European Society of Cardiology Congress 2014
    • Place of Presentation
      Barcelona
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] CGRP受容体と2つのアドレノメデュリン(AM)受容体の異なる活性化機構の同定2013

    • Author(s)
      桑迫健二、北村和雄、永田さやか、加藤丈司
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] G蛋白共役型受容体(GPCR)の重要な細胞内シグナル分子、β-アレスチンの新規作用:1型アドレノメデュリン(AM)受容体の細胞内移行の負の制御2013

    • Author(s)
      桑迫健二、北村和雄、永田さやか、野崎尚美、加藤丈司
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 肥満およびBMIと慢性腎臓病(CKD)発症との関連における性差2013

    • Author(s)
      野村郁夫、小村浩史、北村和雄、桑迫健二、加藤丈司
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 2型アドレノメデュリン受容体の再感作を促進させる一手段2013

    • Author(s)
      桑迫健二、北村和雄、永田さやか、加藤丈司
    • Organizer
      第66回日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] 2型アドレノメデュリン(AM)受容体の再感作促進法の確立2013

    • Author(s)
      桑迫健二、北村和雄、永田さやか、加藤丈司
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] CGRP受容体と2つのアドレノメデュリン(AM)受容体の異なる活性化機構の同定2013

    • Author(s)
      桑迫健二、北村和雄、永田さやか、加藤丈司
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡国際会議場 (京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Novel functions of G protein-coupled receptor kinases: their marked inhibitory effect on adrenomedullin signaling2012

    • Author(s)
      Kenji Kuwasako, Kazuo Kitamura, Sayaka Nagata, Johji Kato
    • Organizer
      24th Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      the Sydney Convention and Exhibition Centre (Sydney, Australia)
    • Related Report
      2012 Research-status Report
  • [Presentation] The third extracellular loop of the human calcitonin receptor-like receptor (CLR) is crucial for the activation of adrenomedullin (AM), but not CGRP, signaling2012

    • Author(s)
      Kenji Kuwasako, Kazuo Kitamura, Sayaka Nagata, Johji Kato
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場 (福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] ARBとカルシウム拮抗薬または利尿薬の併用降圧療法の比較:肥満の有無による降圧効果とアルドステロン濃度変化の差異2012

    • Author(s)
      加藤丈司、桑迫健二、北 俊弘、北村和雄
    • Organizer
      第16回日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      東京大学 (東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 脊索動物におけるCalcitonin (CT) /CT gene-related peptide family の分子進化2012

    • Author(s)
      関口俊男、高橋弘樹、小笠原道生、桑迫健二、笹山雄一、佐竹 炎、鈴木信雄
    • Organizer
      第37回日本比較内分泌学会大会
    • Place of Presentation
      福井大学 (福井)
    • Related Report
      2012 Research-status Report
  • [Presentation] ナメクジウオにおけるカルシトニン受容体と受容体活性調節蛋白(RAMP)の分子機能2012

    • Author(s)
      関口俊男、高橋弘樹、小笠原道生、桑迫健二、鈴木信雄、笹山雄一、佐竹 炎
    • Organizer
      第83回日本動物学会
    • Place of Presentation
      大阪大学 (大阪)
    • Related Report
      2012 Research-status Report
  • [Presentation] アドメノメデュリン(AM)受容体の再感作を促進するストラテジーの確立2012

    • Author(s)
      桑迫健二、北村和雄、永田さやか、野﨑尚美、加藤丈司
    • Organizer
      第35回日本高血圧学会総会
    • Place of Presentation
      名古屋能楽堂 (名古屋)
    • Related Report
      2012 Research-status Report
  • [Presentation] G蛋白共役型受容体キナーゼ(GRK)によるアドメノメデュリン(AM)シグナル抑制2012

    • Author(s)
      桑迫健二、北村和雄、永田さやか、加藤丈司
    • Organizer
      第85回日本内分泌学会総会
    • Place of Presentation
      名古屋国際会議場 (名古屋)
    • Related Report
      2012 Research-status Report
  • [Presentation] アンジオテンシンII産生におけるプロアンジオテンシン-12の役割2012

    • Author(s)
      永田さやか、桑迫健二、北村和雄
    • Organizer
      第85回日本内分泌学会総会
    • Place of Presentation
      名古屋国際会議場 (名古屋)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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