The attenuation mechanism of bradykinin B2 receptor desensitization through prostaglandin EP3 receptor

• Project/Area Number: 20602007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 疼痛学
• Research Institution: Kinjo Gakuin University
• Principal Investigator: KOZAKI Yasuko Kinjo Gakuin University, 薬学部, 准教授 (20126882)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Yayoi 金城学院大学, 薬学部, 教授 (00117847)
• Co-Investigator(Renkei-kenkyūsha): MIZUMURA Kazue 名古屋大学, 環境医学研究所, 教授 (00109349)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: プロスタグランジンEP3受容体 / ブラジキニンB2受容体 / 脱感作 / 痛覚過敏 / 受容体内在化 / インターナリゼーション

Research Abstract

Repeated administration of bradykinin (BK), which is one of the endogenous algesic substances, induces desensitization of B2 receptor. Activation of prostaglandin (PG) E2 EP3 receptor attenuates B2 receptor desensitization, leading to increased pain. Our findings indicate a possibility that prostaglandin enhances both internalization of B2R bound to BK and recycling of the internalized bradykinin B2R through EP3R, and this might be a mechanism for sensitizing the BK response of nociceptors by prostaglandin E2.

Research Products

• [Journal Article] A possible role of prostaglandin in the recycling of internalized bradykinin B2 receptor through EP3 receptor. (Abstract) (2010)
  • Author(s): Kozaki, Y., Suzuki, Y., Katanosaka, K., Mori, M., Mizumura, K.
  • Journal Title: Neuroscience Research Volume: 68(Suppl.1)
• [Journal Article] Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise(delayed onset muscle soreness) (2010)
  • Author(s): Murase., S, Terazawa, E., Queme, F., Hiroki, O., Teru Matsuda, T., Hirate, K., Kozaki, Y., Katanosaka, K., Torn Taguchi, T., Mizumura K.
  • Journal Title: Journal of Neuroscience 30(10) Pages: 3752-3761
  • Peer Reviewed
• [Journal Article] Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed onset muscle soreness. (2009)
  • Author(s): Murase S., Terazawa E., Queme F., Hiroki Ota H., Matsuda T., Hirate K., Kozaki Y., Katanosaka K., Taguchi T., Mizumura K.
  • Journal Title: J.Neurosci. 30(10)
  • Peer Reviewed
• [Journal Article] Excitation and sensitization of nociceptors by bradykinin : What do we know? (2009)
  • Author(s): Mizumura K., Sugiura T., Katanosaka K., Banik R.K., Kozaki Y.
  • Journal Title: Exp.Brain Res. 196(1)(Review)
  • Peer Reviewed
• [Journal Article] Prostaglandin E2 negatively regulates AMP-activated protein kinase via protein kinase A signaling pathway. (2009)
  • Author(s): Funahashi K., Cao X., Yamauchi M., Kozaki Y., Ishiguro N., Kambe F.
  • Journal Title: Prostaglandins & Other Lipid Mediators 88
  • Peer Reviewed
• [Journal Article] Excitation and sensitization of nociceptors by bradykinin : What do we know?(Review) (2009)
  • Author(s): Mizumura, K., Sugiura, T., Katanosaka, K., Banik R.K., Kozaki, Y.
  • Journal Title: Experimental.Brain Research. 196(1) Pages: 53-65
  • Peer Reviewed
• [Journal Article] The bradykinin(BK)-induced desensitization and sequestration of BK B2 receptor is decreased by activation of prostaglandin EP3 receptor (2009)
  • Author(s): Kozaki, Y., Kambe, F., Suzuki, Y., Katanosaka, Mizumura, K.
  • Journal Title: Journal of Physiological Science 59(Suppl.1) Pages: 374-374
• [Journal Article] 3beta-Hydroxysteroid-delta24 reductase is a hydrogen peroxide scavenger, protecting cells from oxidative stress-induced apoptosis. (2008)
  • Author(s): Lu X., Kambe F., Cao X., Kozaki Y., Kaji T., Ishii T., Seo H.
  • Journal Title: Endocrinology 149
  • Peer Reviewed
• [Presentation] プロスタグランジンEP3受容体の活性化による内在化ブラジキニンB2受容体の細胞膜へのリサイクリングの促進 (2011)
  • Author(s): 小崎康子、鈴木義明、片野坂公明、森雅美、水村和枝
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] プロスタグランジンはEP3受容体を介して、内在化したブラジキニンB2受容体のリサイクリングに作用する可能性がある (2010)
  • Author(s): 小崎康子、鈴木義明、片野坂公明、森雅美、水村和枝
  • Organizer: 第33回 日本神経科学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] プロスタグランジンはEP3受容体を介して、内在化したブラジキニンB2受容体のリサイクリングに作用する可能性がある (2010)
  • Author(s): 小崎康子、鈴木義明、片野坂公明、森雅美、水村和枝
  • Organizer: 第33回日本神経科学会
  • Place of Presentation: 神戸
• [Presentation] The bradykinin(BK)-induced desensitization and sequestration of BK B2 receptor is decreased by activation of prostaglandin EP3 receptor (2009)
  • Author(s): Kozaki, Y., Kambe, F., Suzuki, Y., Katanosaka, Mizumura, K.
  • Organizer: 36th International Congress of Physiological Sciences
  • Place of Presentation: 京都
  • Year and Date: 2009-07-29
• [Presentation] The bradykinin (BK)-induced desensitization and sequestration of BK B2 receptor is decreased by activation of prostaglandin EP3 receptor. (2009)
  • Author(s): Kozaki Y., Kambe F., Suzuki Y., Katanosaka, Mizumura K.
  • Organizer: 36th International Congress of Physiological Sciences
  • Place of Presentation: Kyoto
• [Presentation] ブラジキニンB2受容体の脱感作と細胞内移行はプロスタグランジンEP3受容体の活性化により抑制される (2009)
  • Author(s): 小崎康子,神部福司,鈴木義明、片野坂公明、森雅美,水村和枝
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
• [Presentation] 伸張性収縮後にCOX-2 mRNAとNGF mRNA発現増大は異なった時間経過をとる (2008)
  • Author(s): 妹尾詩織、小崎康子、片野坂公明、田口徹、水村和枝
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 伸張性収縮後の筋機械痛覚過敏のB2受容体拮抗薬による抑制の機構 (2008)
  • Author(s): 水村和枝、妹尾詩織、片野坂公明、小崎康子、松田輝
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Remarks] ホームページ等
  • URL: http://www.kinjo-u.ac.jp/kozaki/index.html
• [Remarks]
  • URL: http://www.kinjo-u.ac.jp/kozaki/index.html