Basic research for finding the mechanism of paradox appeared in Controlling asthma

• Project/Area Number: 19590055
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: SAITO Shin-ya University of Shizuoka, 薬学部, 准教授 (80271849)
• Co-Investigator(Kenkyū-buntansha): NAKAHATA Norimichi 東北大学, 大学院・薬学研究科, 教授 (60045804) ; YAMAKUNI Tohru 東北大学, 大学院・薬学研究科, 准教授 (30333793)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 薬理学 / 細胞内情報伝達 / 天然生理活性物質 / 喘息 / 平滑筋 / ホスホジエステラーゼ / 平滑筋収縮 / プロスタノイド / VDCC / カチオンチャネル / アラキドン酸 / cAMP / ホスホエステラーゼ / C1チャネル / PKA

Research Abstract

我々は膜透過性cAMP誘導体およびPDE1阻害薬を使った実験から、cAMPは気管拡張反応を担う重要なセカンドメッセンジャーであるにも関わらず、収縮にも寄与しうることを明らかにした。このことは実は喘息治療薬のパラドックスとして知られている問題の根本には矛盾がないことを示している。今後はどのような条件/細胞内環境がcAMP 機能の切り替えを担っているのかを明らかにすることで、治療薬のより安全な使用方法が確立され得るものと期待される。

Research Products

• [Journal Article] Shishihakuhito, a traditional Chinese medicine for atopic dermatitis, inhibits IgE-mediated histamine release from rat RBL-2H3 basophilic leukocyte cells (2009)
  • Author(s): Wakabayashi M., Sakurai E., Yanai K., Umemura K., Yoshida M., Ohizumi Y., Yamakuni T.
  • Journal Title: J. Trad. Med 26 Pages: 44-49
  • NAID: 110007137398
• [Journal Article] Nobiletin, a citrus flavonoid with neurotrophic action, augments protein kinase A-mediated phosphorylation of the AMPA receptor subunit, GluR1, and the postsynaptic receptor response to glutamate in murine hippocampus (2008)
  • Author(s): Matsuzaki K., Miyazaki K., Sakai S., Yawo H., Nakata N., Moriguchi S., Fukunaga K., Yokosuka A., Sashida Y., Mimaki Y., Yamakuni T., Ohizumi Y.
  • Journal Title: Eur J Pharmacol 578 Pages: 194-200
• [Journal Article] βγ subunits of Gi/o suppress epidermal growth factor-induced phosphorylation of extracellular signal-regulated kinase 5, whereas they enhance phosphorylation of extracellular-signal regulated kinase 1/2 (2008)
  • Author(s): Obara Y., Okano Y., Ono S., Yamauchi A., Hoshino T., Kurose H., Nakahata N.
  • Journal Title: Cell. Signal 20 Pages: 1275-1283
• [Journal Article] Nobiletin, a citrus flavonoid, reverses learning impairment associated with NMDA receptor antagonism by activation of ERK signaling (2007)
  • Author(s): Nakajima A., Yamakuni T., Matsuzaki K., Nakata N., Onozuka H., Yokosuka A., Sashida Y., Yoshihiro Mimaki Y., Ohizumi Y.
  • Journal Title: J. Pharmacol. Exp. Ther 321 Pages: 784-790
• [Journal Article] Distinct effects of Z-335, a new thromboxane A_2 receptor antagonist, on rabbit platelets and aortic smooth muscles (2007)
  • Author(s): Yoshida M., Sato Y., Shimura T., Ohkubo S., Honma S., Tanaka T., Kurimoto T., Nakahata N.
  • Journal Title: Pharmacology 79 Pages: 50-56
• [Journal Article] Low expression of cell-surface thromboxane A_2 receptor b-isoform through the negative regulation of its membrane traffic by proteasomes (2007)
  • Author(s): Sasaki M., Sukegawa J., Miyosawa K., Yanagisawa T., Ohkubo S., Nakahata N.
  • Journal Title: Prostagland. Other Lipid Mediat 83 Pages: 237-249
• [Journal Article] Piperlongmine, a constituent of Piper longum L., inhibits rabbit platelet aggregation as a thromboxane A2 recepter antagonist (2007)
  • Author(s): Iwashita M., Oka N., Ohkubo S., Saito M., Nakahata N.
  • Journal Title: Eur. J. Pharmacol 570 Pages: 38-42
• [Journal Article] Mastoparan inhibits β-adrenoceptor-Gs signaling by changing the localization of Gas in lipid rafts (2007)
  • Author(s): Sugama J., Yu J.-Z., Rasenick M.M., Nakahata N.
  • Journal Title: Cell. Signal 19 Pages: 2247-2254
• [Journal Article] Alteration of adenylyl cyclase type 6 expression in human astrocytoma cells after exposure to simulated microgravity (2007)
  • Author(s): Matsuoka R., Ohkubo S., Yoshida M. Nakahata N.
  • Journal Title: J. Health Sci 53 Pages: 534-542
  • NAID: 110006402639
• [Journal Article] Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins (2007)
  • Author(s): Ikeda A, et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 363 Pages: 835-839
  • Peer Reviewed
• [Presentation] Contribution of phospholipase A_2 to U46619-induced vascular contraction in rat aorta (2009)
  • Author(s): Suzuki K., Nishijima A., Saito S., Ishikawa T.
  • Organizer: 第82回日本薬理学会年会(J. Pharmacol. Sci.)
  • Place of Presentation: 横浜(109(Supl. 1))
  • Year and Date: 2009-03-17
• [Presentation] ラット大動脈U46619誘発性血管収縮反応におけるホスホリパーゼA_2の関与 (2009)
  • Author(s): 鈴木公章
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-17
• [Presentation] The role of phospholipase A_2 product in U46619-induced contraction mediated by voltage dependent Ca^<2+> channel in the presence of indomethacin (2008)
  • Author(s): Nishijima A., Saito S., Ishikawa T.
  • Organizer: 第81回日本薬理学会年会(J. Pharmacol. Sci.)
  • Place of Presentation: 横浜(106(Supl. 1))
  • Year and Date: 2008-03-17
• [Presentation] インドメタシン存在下で電位依存性Caチャネルを介するU46619誘発性収縮におけるホスホリパーゼA_2産生物の役割 (2008)
  • Author(s): 西島愛美
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Book] Toxins affecting actin filaments and microtubules. In Marine Toxins as Research Tools. (Fusetani N. and Kem W. eds.) (2009)
  • Author(s): Saito S
  • Publisher: Springer-Verlag
• [Book] Marine Toxins as Research Tools(Nobuhiro Fusetani and William Kem eds. ) (2009)
  • Author(s): Shin-ya Saito
  • Publisher: Springer-Verlag