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Basic and clinical studies of the adrenomedullin receptor

Research Project

Project/Area Number 15K09124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular 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) 北村 和雄  宮崎大学, 医学部, 教授 (50204912)
永田 さやか  宮崎大学, 医学部, 助教 (00452920)
加藤 丈司  宮崎大学, フロンティア科学実験総合センター, 教授 (20274780)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsペプチド / G蛋白共役型受容体 / 心血管病 / 分子調節機構 / 臨床応用
Outline of Final Research Achievements

Adrenomedullin (AM) is a potent hypotensive peptide and can mediate multi-protective signaling through type 1 AM receptors (AM1 receptors), which consist of calcitonin receptor-like receptor (CLR), a G protein-coupled receptor (GPCR), and GPCR activity-modifying protein 2 (RAMP2). Here we elucidated the molecular basis and mechanism of GPCR kinases (GRKs) and beta-arrestins, both of which interact with the cytoplasmic C-terminal tail of the human (h)AM1 receptors. We also clarified the molecular mechanism by which protein kinase C (PKC) induces the internalization of the hAM1 receptors in the absence of AM. Furthermore, we elucidated the mechanism of the intracellular trafficking and signaling of the hAM1 receptors using their stable transfectants and found an effective strategy that can promote their re-sensitization.

Report

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

    (32 results)

All 2017 2016 2015

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Acknowledgement Compliant: 8 results,  Open Access: 5 results) Presentation (21 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Beta-arrestins negatively control human adrenomedullin type 1-receptor internalization.2017

    • Author(s)
      Kuwasako K, Kitamura K, Nagata S, Sekiguchi T, Jiang D, Murakami N, Hattori Y, Kato J
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 印刷中 Issue: 2 Pages: 438-443

    • DOI

      10.1016/j.bbrc.2017.04.083

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Calcitonin-typical suppression of osteoclastic activity by amphioxus calcitonin superfamily peptides and insights into the evolutionary conservation and diversity of their structures.2017

    • Author(s)
      Sekiguchi, T., Shiraishi, A., Satake, H., Kuwasako, K., Takahashi, H., Sato, M., Urata, M., Wada, S., Endo, M., Ikari, T., Hattori, A., Srivastav, A.K. and Suzuki, N.
    • Journal Title

      Gen. Comp. Endocrinol.

      Volume: 246 Pages: 294-300

    • DOI

      10.1016/j.ygcen.2017.01.004

    • NAID

      120005973614

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inhibitory effects of losartan and azelnidipine on augmentation of blood pressure variability induced by angiotensin II in rats.2017

    • Author(s)
      Jiang D, Kawagoe Y, Kuwasako K, Kitamura K, Kato J
    • Journal Title

      Eur J Pharmacol

      Volume: 印刷中 Pages: 91-95

    • DOI

      10.1016/j.ejphar.2017.04.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Plasma levels of natriuretic peptides and year-by-year blood pressure variability: a population-based study2017

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

      J Hum Hypertens

      Volume: 印刷中 Issue: 8 Pages: 525-529

    • DOI

      10.1038/jhh.2017.14

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Augmented blood pressure variability in hypertension induced by angiotensin II in rats2017

    • Author(s)
      Jiang D, Kawagoe Y, Kuwasako K, Kitamura K, Kato J
    • Journal Title

      Eur J Pharmacol

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
  • [Journal Article] Inhibitory effects of two G protein-coupled receptor kinases on the cell surface expression and signaling of the human adrenomedullin receptor.2016

    • Author(s)
      Kuwasako, K., Sekiguchi, T., Nagata, S., Jiang, D., Hayashi, H., Murakami, M., Hattori, Y., Kitamura, K. and Kato, J.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 470 Issue: 4 Pages: 894-899

    • DOI

      10.1016/j.bbrc.2016.01.138

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evidence for conservation of the calcitonin superfamily and activity-regulating mechanisms in the basal chordate Branchiostoma floridae: insight into the molecular and functional evolution in chordates.2016

    • Author(s)
      Sekiguchi, T., Kuwasako, K., Ogasawara, M., Takahashi, H., Matsubara, S., Osugi, T., Muramatsu, I., Sasayama, Y., Suzuki, N., and Satake, H.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 5 Pages: 2345-2356

    • DOI

      10.1074/jbc.m115.664003

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Augmented blood pressure variability in hypertension induced by angiotensin II in rats.2016

    • Author(s)
      Jiang D, Tokashiki M, Hayashi H, Kawagoe Y, Kuwasako K, Kitamura K, Kato J.
    • Journal Title

      Am J Hypertens

      Volume: 29 Issue: 2 Pages: 163-169

    • DOI

      10.1093/ajh/hpv102

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Plasma levels of natriuretic peptides and development of chronic kidney disease2015

    • Author(s)
      Ogawa N, Komura H, Kuwasako K, Kitamura K, Kato J
    • Journal Title

      BBMC Nephrol

      Volume: 16 Issue: 1 Pages: 171-176

    • DOI

      10.1186/s12882-015-0163-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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 Issue: 1 Pages: 43-49

    • DOI

      10.1530/ec-14-0131

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.2015

    • 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 Issue: 3 Pages: 584-589

    • DOI

      10.1016/j.bbrc.2015.02.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] G 蛋白共役型受容体(GPCR)を制御するシグナル分子、GPCR キナーゼとβ-アレスチンの1型アドレノメデュリン(AM)受容体の細胞内輸送機構における新規作用2017

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜 丹鳳、加藤丈司
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] カルシトニン(CT)/CT遺伝子関連ペプチド(CGRP)ファミリーの起源のペプチドと受容体の同定と機能解析2017

    • Author(s)
      桑迫健二、関口俊男、姜 丹鳳、加藤丈司、鈴木信雄、佐竹 炎
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Presentation] 地元自治体健診における過去24年間の高血圧および心血管危険因子コントロール状況と高血圧対策の今後の課題2017

    • Author(s)
      加藤丈司、姜 丹鳳、桑迫健二、渡嘉敷真理子、北村和雄
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 地元自治体における24年間の健診結果の解析と今後の課題2017

    • Author(s)
      加藤丈司、桑迫健二、北村和雄
    • Organizer
      第6回臨床高血圧フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血中ナトリウム利尿ペプチド(ANP、BNP)レベルと長期血圧変動性の関連2017

    • Author(s)
      加藤丈司、川越由紀子、姜 丹鳳、桑迫健二、渡嘉敷真理子、北村和雄
    • Organizer
      第21回日本心血管内分泌代謝学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血圧変動性増大の動物モデルと病態薬理学的解析2017

    • Author(s)
      姜 丹鳳、渡嘉敷真理子、川越由紀子、桑迫健二、北村和雄、加藤丈司
    • Organizer
      第53回高血圧関連疾患モデル学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ナトリウム利尿ペプチドの血漿濃度と慢性腎臓病(CKD)発症との関連について2016

    • Author(s)
      小川敬之、小村浩史、桑迫健二、北村和雄、加藤丈司
    • Organizer
      第5回臨床高血圧フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2016-05-15
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト1型アドレノメデュリン受容体(AM1受容体)の新規作用:AM非刺激下のプロテインキナーゼC(PKC)の活性化による細胞内移行の促進2016

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜丹鳳、林英孝、加藤丈司
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞内シグナル分子、β-アレスチンの新規作用2016

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜 丹鳳、加藤丈司
    • Organizer
      第69回日本薬理学会西南部会
    • Place of Presentation
      愛媛
    • Related Report
      2016 Research-status Report
  • [Presentation] カルシトニン(CT)/CT遺伝子関連ペプチド(CGRP)ファミリーの進化研究:その起源のペプチドと受容体の同定と機能解析2016

    • Author(s)
      桑迫健二、関口俊男、永田さやか、姜 丹鳳、北村和雄、加藤丈司、鈴木信雄、佐竹 炎
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
  • [Presentation] アンジオテンシンII(Ang II)持続投与による血圧変動性増大に対するジヒドロピリジン系2016

    • Author(s)
      姜 丹鳳、川越由紀子、桑迫健二、北村和雄、加藤丈司
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
  • [Presentation] 一般住民におけるアドレノメデュリン(AM)の血中濃度の性差および体重増加との関連2016

    • Author(s)
      河野清香、川越由紀子、桑迫健二、渡嘉敷真理子、北村和雄、加藤丈司
    • Organizer
      第113回日本内科学会講演会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] アンジオテンシンII持続投与高血圧ラットの血圧変動性増大2015

    • Author(s)
      姜 丹鳳、渡嘉敷真理子、林英孝、川越由紀子、桑迫健二、北村和雄、加藤丈司
    • Organizer
      第19回日本心血管内分泌代謝学会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 一般住民における血中アドレノメデュリン値の性差および体重増加との関連2015

    • Author(s)
      河野清香、川越由紀子、桑迫健二、島本怜史、五十嵐浩二、渡嘉敷真理子、北村和雄、加藤丈司
    • Organizer
      第19回日本心血管内分泌代謝学会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] G蛋白共役型受容体キナーゼ(GRK)の新規作用:降圧系1型アドレノメデュリン受容体(AM1受容体)の細胞膜輸送の強力な抑制効果2015

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜 丹鳳、林 英孝、加藤丈司
    • Organizer
      第19回日本心血管内分泌代謝学会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] G蛋白共役型受容体キナーゼ(GRK)の新規作用2015

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜 丹鳳、加藤丈司
    • Organizer
      第68回日本薬理学会西南部会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトI型アドレノメデュリン(AM)受容体のAM非刺激下の新規作用:プロテインキナーゼC(PKC)の活性化による細胞内移行の促進2015

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜丹鳳、林 英孝、渡嘉敷真理子、加藤丈司
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛県県民文化会館(愛媛県松山市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] アンジオテンシンII持続投与高血圧ラットの血圧変動性増大2015

    • Author(s)
      姜丹鳳、渡嘉敷真理子、林 英孝、川越由紀子、桑迫健二、北村和雄、加藤丈司
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛県県民文化会館(愛媛県松山市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] N端パルミトイル化アドレノメデュリン誘導体の臨床応用に向けた有用性2015

    • Author(s)
      渡嘉敷真理子、久保恵是、桑迫健二、永田さやか、加藤丈司、北村和雄
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛県県民文化会館(愛媛県松山市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] G蛋白共役型受容体キナーゼ(GRK)によるアドレノメデュリン(AM)受容体の細胞膜輸送の抑制効果2015

    • Author(s)
      桑迫健二、北村和雄、永田さやか、姜丹鳳、林英孝、加藤丈司
    • Organizer
      第66回日本薬理学会北部会
    • Place of Presentation
      富山国際会議場(富山県富山市)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Biochemical properties of the N-terminally palmitoylated adrenomedullin2015

    • Author(s)
      Mariko Tokashiki, Kubo Keishi, Kenji Kuwasako, Sayaka Nagata, Johji Kato,Kazuo Kitamura
    • Organizer
      2015 Council on Hypertension
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2015-09-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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