Anti-MR(mineralocorticoid receptor) effect of dihydropyridine Ca channel blocker.

• Project/Area Number: 21790897
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Endocrinology
• Research Institution: Keio University
• Principal Investigator: KURIHARA Isao 慶應義塾大学, 医学部, 講師 (90338038)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 高血圧 / アルドステロン(ミネラルコルチコイド) / ステロイドホルモン受容体 / Ca拮抗薬 / 循環器・高血圧 / ジヒドロピリジン系Ca拮抗薬 / ミネラルコルチコイド受容体

Research Abstract

The study revealed that anti-MR effect of dihydropyridine Ca channel blocker(dpCCB) can be observed in vivo(in human). We also demonstrated that dpCCB antagonized not only MR but also other steroid hormone receptors such as glucocorticoid receptor and progesterone receptor partly and in diverse manner. This finding should have great impact as a translational research in that dpCCB is one of the most commonly used antihypertensives and we demonstrated a novel beneficial aspect of this agents.

Research Products

• [Journal Article] Coactivation of SF-1-Mediated Transcription of Steroidogenic Enzymes by Ubc9 and PIAS1 (2011)
  • Author(s): Suda N, Shibata H, Kurihara I, Ikeda Y, Kobayashi S, Yokota K, Murai-Takeda A, Nakagawa K, Oya M, Murai M, Rainey WE, Saruta T, Itoh H
  • Journal Title: Endocrinology Volume: 152(6) Pages: 2266-77
  • Peer Reviewed
• [Journal Article] Coactivation of SF-1-Mediated Transcription of Steroidogenic Enzymes by Ubc9 and PIAS1. (2011)
  • Author(s): Suda N, Shibata H, Kurihara I, et al
  • Journal Title: Endocrinology Volume: Epub
  • Peer Reviewed
• [Journal Article] NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor (2010)
  • Author(s): Murai-Takeda A, Shibata H, Kurihara I, Kobayashi S, Yokota K, Suda N, Mitsuishi Y, Jo R, Kitagawa H, Kato S, Saruta T, Itoh H
  • Journal Title: J Biol Chem Volume: 285(11) Pages: 8084-93
  • Peer Reviewed
• [Journal Article] Gastrointestinal pseudo-obstruction after debulking surgery of malignant pheochromocytoma, improved by intravenous administration of alpha-adrenergic receptor blocker, phentolamine (2010)
  • Author(s): Yamaguchi S, Shibata H, Miyashita K, Kurihara I, Murai-Takeda A, Mitsuishi Y, Motosugi Y, Saito Y, Hayashi K, Itoh H
  • Journal Title: Hypertens Res Volume: 33(7) Pages: 753-4
  • Peer Reviewed
• [Journal Article] NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor. (2010)
  • Author(s): Murai-Takeda A, Shibata H, Kurihara I, et al
  • Journal Title: J Biol Chem Volume: 285(11) Pages: 8084-93
  • Peer Reviewed
• [Presentation] 核内受容体と内分泌代謝疾患Update治療抵抗性高血圧におけるミネラルコルチコイド受容体の蛋白修飾による活性化機構 (2011)
  • Author(s): 柴田洋孝, 栗原勲, 三石木綿子, 林毅, 城理絵, 横田健一, 武田彩乃, 本杉裕一郎, 大山貴子, 伊藤裕
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-23
• [Presentation] 術前検査で褐色細胞腫が疑われ、病理所見で多発する血管腫が確認された、石灰化を伴う副腎偶発腫瘍の一例 (2011)
  • Author(s): 栗原勲, 他
  • Organizer: 第84回日本内分泌学会総会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2011-04-23
• [Presentation] 原発性アルドステロン症の病型診断における血中18-水酸化ステロイド測定の有用性 (2010)
  • Author(s): 栗原勲, 柴田洋孝, 武田彩乃, 三石木綿子, 本杉裕一郎, 林毅, 城理絵, 宮下和季, 本間桂子, 伊藤裕
  • Organizer: 日本ステロイドホルモン学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-27
• [Presentation] Pancreatic solid-pseudopapillary tumorが疑われた副腎偶発腫瘍の一例 (2010)
  • Author(s): 栗原勲, 他
  • Organizer: 日本内分泌病理学会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-30
• [Presentation] Dihydropyridine calcium channel blockers have selective antagonist activity of steroid hormone receptors through blocking nuclear translocation of the receptor (2010)
  • Author(s): Isao Kurihara, Hirotaka Shibata, Yuko Mitsuishi, Ayano Murai-Takeda, Yuichiro Motosugi, Takashi Hayashi, Rie Jo, Hiroshi Itoh
  • Organizer: 国際内分泌学会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-29
• [Presentation] Dihydropyridine calcium channel blockers have selective antagonist activity of steroid hormone receptors through blocking nuclear translocation of the receptor. (2010)
  • Author(s): Lsao Kurihara, et al.
  • Organizer: ICE 2010(国際内分泌学会2010)
  • Place of Presentation: 京都国際会館
  • Year and Date: 2010-03-28
• [Presentation] EGFによるミネラルコルチコイド受容体のアルドステロン感受性亢進の分子機構治療抵抗性高血圧における役割 (2010)
  • Author(s): 三石木綿子, 柴田洋孝, 栗原勲, 横田健一, 武田彩乃, 城理絵, 林毅, 本杉裕一郎, 伊藤裕
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-26
• [Presentation] ジヒドロピリジン系Ca拮抗薬はCaチャンネル作用とは独立した新規ミネラルコルチコイド受容体拮抗作用を有する (2009)
  • Author(s): 栗原勲, 柴田洋孝, 三石木綿子, 武田彩乃, 本杉裕一郎, 伊藤裕
  • Organizer: 日本高血圧学会
  • Place of Presentation: 大津
  • Year and Date: 2009-10-01
• [Presentation] ジヒドロピリジン系Ca拮抗薬はCaチャンネル拮抗作用とは独立した新規ミネラルコルチコイド受容体拮抗作用を有する (2009)
  • Author(s): 栗原勲, 他
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津プリンス(滋賀)
  • Year and Date: 2009-10-01
• [Presentation] ジヒドロピリジン系Ca拮抗薬のミネラルコルチコイド受容体拮抗作用の検討 (2009)
  • Author(s): 栗原勲、柴田洋孝、三石木綿子、横田健一、武田彩乃、本杉裕一郎、林毅、城理絵、伊藤裕
  • Organizer: 東京アルドステロンフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2009-07-17
• [Presentation] レニン・アンジオテンシン・アルドステロン系の新展開ジヒドロピリジン系Ca拮抗薬のミネラルコルチコイド受容体拮抗作用の検討 (2009)
  • Author(s): 栗原勲, 柴田洋孝, 三石木綿子, 武田彩乃, 本杉裕一郎, 伊藤裕
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 前橋
  • Year and Date: 2009-04-23