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1990 Fiscal Year Final Research Report Summary

Pharmacological Response of Smooth Muscle is related With its Myosin Phosphorylation.

Research Project

Project/Area Number 63480475
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionGunma University (1989)
The University of Tokyo (1988)

Principal Investigator

KOHAMA Kazuhiro  Gunma University, School of Medicine, Department of Pharmacology, Professor, 医学部, 教授 (30101116)

Co-Investigator(Kenkyū-buntansha) TAKANO-OHMURO Hiromi  Tokyo Metropolitan Institute of Medical Science, Researcher, 炎症部門, 研究員 (00124470)
Project Period (FY) 1988 – 1989
Keywordsactomyosin / myosin / phosphorylation / kinase / phosphatase / electrophoresis / myosin light chain / 電気泳動
Research Abstract

NA0344, a novel derivative of antibiotics, inhibited phosphorylation of 20,000 Mr myosin light chain (LC) of smooth muscle native actomyosin containing both phosphotase and calmodulin/myosin LC kinas (MLCK) activity (IC_<50> = 6.2 x 10^<-6> g/ml). The inhibitory effect is attributable to the direct inhibition of MLCK.
NA0344 also inhibited actin-myosin-ATP interaction of the native actomyosin with IC_<50> = 3.7 x 10^<-7> and 3.8 x 10^<-7> g/ml as monitored by superprecipitation and ATPase activity, respectively.
Thoretically, myosin whose phosphorylation is partially inhibited by NA0344 comprises from unphosphorylated myosin, heterodimer myosin isoform with an unphosphorylated LC and a phosphorylated LC, and homodimer myosin isoform with both LC phosphorylated. We have developed the analytical electrophoresis separating these isomers and found that IC_<50> for the homodimer in native actomyosin was at the level of 10^<-7> g/ml. If we assume that only the homodimer is active in actin-myosin-ATP interaction, inhibition of the interaction can be explatined by that of myosin phosphorylation with MLCK.
Recently, okadaic acid has been reported to enhance actin-myosin-ATP interaction. The effect is interpreted to be mediated by inhibiting phosphatase activity resulting in the enhancement of phosphorylation. We succeeded in preparing the native actomyosin which does not contain phosphatase activity. With this preparation, the enhancing effect was observed, indicating that okadaic acid enhances the interaction directly through myosins.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Ozaki,H.,Moriyama,T.,Karaki,H.,Kohama,K.and Cragoe Jr.E.J.: "Direct inhibition of contractile apparatus by analoques of amiloride in the smooth muscle of quinea‐pig taenia caecum and chicken qizzard" Biochem.pharmacol.38. 915-922 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] TakanoーOhmuro,H.,Kohama,K.,Kathuria,S.and FujitaーYamaquchi,Y.: "Insulin receptor phosphorylates qizzard smooth muscle myosin light chain in vitro" Proc.Japan Acad.65,Ser.B. 199-202 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lin,Y.,TakanoーOhmuro,H.and Kohama,K.: "Myosin Iーlike protein in qizzard smooth muscle" Proc.Japan Acad.65,Ser.B. 202-203 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayakawa,K.,Dobashi,T.,Sakanishi,A.,Iwai,T.and Kohama,K.: "Effect of okadaic acid on MgーATPase activity of native actomyosin or smooth mode;enhancement of the activity without altering extert of phosphorylation of myosin liqht chain" Rep.Proq.Polymer Phys.Japan. 33. 619-620 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kohama,K.,TakanoーOhmuro,H.,Sohda,M.,Ozaki,H.,Karaki,H.,Hiranuma,T.and Hachisu,M.: "Effects of NA0344,a new antihypertensive,on the actinーmyosinーATP interaction and myosin liqht chain phosphorylation in vitro" Gen.Pharmac.22. 465-474 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kohama,K.,TakanoーOhmuro,H.,Sohda,M.,Hiranuma,T.and Hachisu,M.: "Proqress in Clinical and Bioloqical Research,Vol.315;"MUSCLE ENERGETICS"(paul,R.J.,Elzinga,G.and Yamada,K.,eds.)" Alan R.Liss,Inc.,New York, 100-103 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小浜 一弘: "平滑筋のactomyoinと制御蛋白質“カルシウムと情報伝達系"(浦川紀元,磨木英明編" 文永堂出版, (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozaki, H., Kojima, T., Moriyama, T., Karaki, H., Urakawa, N., Kohama, K. and Nonomura, Y.: "Inhibition by amiloride of contractile elements in smooth muscle of quinea pig taenia cecum and chicken gizzard." J. Pharmacol. & Exp. Ther.243, (1). 370-377 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki, H., Ishihara, H., Kohama, K., Nonomura, Y., Shibata, S. and Karaki, H.: "Calcium-independent phosphorylation of smooth muscle myosin light chain by Okadaic acid isolated from black sponge (Halichondria okadai)." J. Pharmacol. & Exp. Ther.243, (3). 1167-1173 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takano-Ohmuro, H. and Kohama, K.: "Native pyrophosphate gel analysis of smooth muscle myosin phosphorylated with protein kinase C." J. Biochem.102. 971-974 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozaki, H., Moriyama, T., Karaki, H., Kohama, K. and Cragoe Jr, E. J.: "Direct inhibition of contractile apparatus by analogues of amiloride in the smooth muscle of guinea-pig taenia caesium and chicken gizzard." Biochem. Pharmacol. 38, (6). 915-922 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohama, K., Takano-Ohmuro, H., Sohda, M., Hiranuma, T. and Hachisu, M.: "Inhibition of actin-myosin-ATP interaction of smooth muscle native actomyosin is not closely associated with inhibition of its myosin light chain phosphorylation : studies with derivatives of antibiotic SF-2370." Progress in Clinical and Biological Research, Vol. 315 : "MUSCLE ENERGETICS" (Paul, R. J., Elzinga, G. and Yamada, K., eds.) Alan R. Liss, Inc., New York. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takano-Ohmuro, H., Kohama, K., Kathuria, S. and Fujita-Yamaguchi, Y.: "Insulin receptor phosphorylates gizzard smooth muscle myosin light chain in vitro." Proc. Japan Acad.65, Ser. B. 199-202 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lin, Y., Takano-Ohmuro, H. and Kohama, K.: "Myosin I-like protein in gizzard smooth muscle." Proc. Japan Acad.65, Ser. B. 207-210 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayakawa, K., Dobashi, T., Sakanishi, A., Iwai, T. and Kohama, K.: "Effect of okadaic acid on Mg-ATPase activity of native actomyosin or smooth mode : enhancement of the activity without altering extert of phosphorylation of myosin light chain." Rep. Prog. Polymer Phys. Japan. 33. 619-620 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohama, K., Takano-Ohmuro, H., Sohda, M., Ozaki, H., Karaki, H., Hiramura, T. and Hachisu, M.: "Effects of NA0344, a new antihypertensive, on the actin-myosin-ATP interaction and myosin light chain phosphorylation in smooth muscle : dissociation of the effects." Gen. Pharmac. 22. 465-471 (1991)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-08-12  

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