Clarification of the mechanism of a novel inhibitory effect on platelet aggregation via prostaglandin E_2 receptor

• Project/Area Number: 22790241
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General pharmacology
• Research Institution: Asahikawa Medical College
• Principal Investigator: KASHIWAGI Hitoshi 旭川医科大学, 医学部, 助教 (60510609)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 心血管 / 血液 / 血小板 / プロスタグランジンE2 / EP2受容体 / EP4受容体 / 受容体欠損マウス / プロスタグランジンE_2 / EP_2受容体 / EP_4受容体

Research Abstract

In this study, it was suggested that selective activation of prostaglandin E_2 receptor subtype EP_2 or EP4 showed the inhibitory effect on platelet aggregation. Notably, an EP_4 agonist can inhibit human platelet aggregation with high potency, suggesting a potential of EP_4 agonists as novel anti-platelet agents.

Research Products

• [Journal Article] エイコサノイド (2012)
  • Author(s): 結城幸一
  • Journal Title: 臨床検査 Volume: 第56巻 Pages: 145-150
• [Journal Article] Roles of prostanoids in the pathogenesis of cardiovascular diseases : Novel insights from knockout mouse studies (2011)
  • Author(s): Koh-ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, 他4名
  • Journal Title: Pharmacology and Therapeutics Volume: Vol.129 Pages: 195-205
  • Peer Reviewed
• [Journal Article] プロスタノイド受容体ノックアウトマウス (2011)
  • Author(s): 結城幸一
  • Journal Title: The Lipid Volume: Vol.22 Pages: 4-11
• [Journal Article] Roles of prostanoids in the pathogenesis of cardiovascular diseases : Novel insights from knockout mouse studies (2011)
  • Author(s): Koh-ichi Yuhki
  • Journal Title: Pharmacology and Therapeutics Volume: Volume 129 Pages: 195-205
  • Peer Reviewed
• [Journal Article] Selective activation of the prostaglandin E_2 receptor subtype EP_2 or EP_4 leads to inhibition of platelet aggregation (2010)
  • Author(s): Shuhko Kuriyama, Hitoshi Kashiwagi (These authors contributed equally to this work.), 他10名
  • Journal Title: Thrombosis and Haemostasis Volume: Vol.104 Pages: 796-803
  • Peer Reviewed
• [Journal Article] Selective activation of the prostaglandin E_2 receptor subtype EP_2 or EP_4 leads to inhibition of platelet aggregation (2010)
  • Author(s): Shuhko Kuriyama, Hitoshi Kashiwagi
  • Journal Title: Thrombosis and Haemostasis Volume: Volume 104 Pages: 796-803
  • Peer Reviewed
• [Journal Article] The intrinsic prostaglandin E_2-EP_4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice
  • Author(s): Naoki Nakagawa, 他13名
  • Journal Title: Kidney International Volume: (in press)
  • Peer Reviewed
• [Journal Article] The intrinsic prostaglandin E_2-EP_4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice
  • Author(s): Naoki Nakagawa
  • Journal Title: Kidney International Volume: (in press)
  • Peer Reviewed
• [Presentation] Inhibition of thromboxane A_2 synthase prevents reduction in the anti-platelet effect of a prostaglandin I_2 receptor agonist after repeated administration (2012)
  • Author(s): Hitoshi Kashiwagi
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2012-03-14
• [Presentation] トロンボキサンA_2合成酵素の阻害はプロスタグランジンI_2受容体の脱感作を抑制する (2011)
  • Author(s): 柏木仁
  • Organizer: 第62回日本薬理学会北部会
  • Place of Presentation: 江陽グランドホテル(宮城県)
  • Year and Date: 2011-09-30
• [Presentation] 、プロスタグランジンE_2受容体サブタイプEP_4の抗血小板療法ターゲットとしての可能性 (2010)
  • Author(s): 柏木仁
  • Organizer: 第20回日本循環薬理学会
  • Place of Presentation: 札幌市教育文化会館(北海道)
  • Year and Date: 2010-11-11
• [Presentation] プロスタグランジンE_2受容体サブタイプEP_4の抗血小板療法ターゲットとしての可能性 (2010)
  • Author(s): 柏木仁
  • Organizer: 第20回日本循環薬理学会
  • Place of Presentation: 札幌市教育文化会館(北海道)
  • Year and Date: 2010-11-11
• [Presentation] Prostaglandin E_2 receptor subtype EP_2 and EP_4 emerge as novel targets for anti-platelet therapy (2010)
  • Author(s): Hitoshi Kashiwagi
  • Organizer: 2010 Keystone Symposia (Bioactive Lipids : Biochemistry and Diseases)
  • Place of Presentation: ウェスティン都ホテル京都(京都府)
  • Year and Date: 2010-06-08