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Effects of marine toxins on smooth muscle contractile mechanism

Research Project

Project/Area Number 63480088
Research Category

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

Allocation TypeSingle-year Grants
Research Field 基礎獣医学
Research InstitutionDepartment of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo

Principal Investigator

KARAKI Hideaki  Dept of Vet Pharmacol, Fac of Agr, Univ of Tokyo, 農学部, 教授 (60011912)

Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsSmooth Muscle / Contractile proteins / Okadaic acid / Calyculin A / Phosphatase inhibitor / 脱リン酸化酵素
Research Abstract

Okadaic acid (OA)^2 and calyculin A (CLA) are toxins isolated from marine sponges. OA at lower concentrations inhibited the contractions in smooth muscle and at higher concentrations it induced a contraction. By contrast, CLA at lower concentrations transiently relaxed and then contracted smooth muscle. Both OA and CLA increased cytosolic Ca^<2+> levels which occurred after the development of muscle contraction. Contractions induced by these toxins were not inhibited in the absence of external Ca^<2+>, suggesting that contraction induced by these toxins is not attributable to the increase in cytosolic Ca^<2+> level. The contraction induced by OA and CLA followed the increase in myosin light chain phosphorylation which was not inhibited by Ca^<2+> -removal or calmodulin inhibitors. These toxins did not directly activate myosin light chain kinase or C kinase. Howver, OA at lower concentrations inhibited type 2A protein phosphatase and at higher concentrations it also inhibited type 1 phosphatase. By contrast, CLA at lower concentrations inhibited both type 2A and type 1 phosphatases. Phosphatase isolated from smooth muscle was inhibited by higher concentrations of OA and by lower concentrations of CLA, suggesting that phosphatase in smooth muscle is type 2A. However, smooth muscle phosphatase was not inhibited by "Inhibitor 2", indicating that it belongs to type 2A. OA and CLA may inhibit this phosphatase and increase relative activity of Ca^<2+> - and calmodulin-independent myosin light chain kinase to induce contraction. Since the inhibitory effect of lower concentrations of OA was similar to that of cyclic AMP, lower concentrations of OA may inhibit the phosphatase which antagomizes the effect of cyclic AMP-dependent protein kinase to induce smooth muscle relaxation.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Ozaki H.,Ishihara H.,Kohama K.,Nonomura Y.,Shibata S.,Karaki H.: "Calcium-independent phosphorylation of smooth muscle myosin light chain by okadaic acid isolated from black sponge" Journal of Pharmacology and Experimental Therapeubics. 243. 1167-1173 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishihara H.,Martin BL,Braughfigan DL,Karaki H.,Ozaki H.,Kato Y.,Fusetani N.,Watabe S.,Hashimoto K.,Uemura D.,Hartshorne DJ.: "Calyculin A and okadaic acid:Inhibitors of protein phosphatase activity" Biochemical and Biophysical Research Communications. 159. 871-877 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hartshorne DJ,Ishihara H.,Karaki H.,Ozaki H.,Sato K.,Hori M.,Watabe S.,: "Okadaic acid and calyculin A:Effects on smooth muscle systems." Advance in Protein Phosphatases. 5. 219-231 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Karaki H.,Mitsui M.,Nagase H.,Ozaki H.,Shibata S.,Uemura D.: "Inhibitory effect of a toxin okadaic acid isolated from the black sponge on smooth muscle and platelets" British Journal of Pharmacology. 98. 590-596 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishihara H.,Ozaki H.,Sato K.,Hori M.,Karaki H.,Watabe S.,Kato Y.,Fusetani N.,Hashimoto K.,Uemura D.and Hartshorne DJ.: "Calcium-independent activation of contractile apparatus in smooth muscle by calyculin A" Journal of Pharmacology and Experimental Therapeutics. 250. 388-396 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 柴田章次,児玉逸雄,唐木英明: "Okadaic acidの平滑筋および心筋への作用" 実験医学. 印刷中. (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ozaki H, Ishihara H, Kohama K, Nonomura Y, Shibata S, Karaki H.: "Calcium-independent phosphorylation of smooth muscle myosin light chanin by okadaic acid isolated from black sponge (Harichondria okadai)." Journal of Pharmacology and Experimental Therapeutics 243, 1167-1173, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishihara, H, Martin BL, Brautigan DL, Karaki H, Ozaki H, Kato Y, Fusetani N, Watabe S, Hashimoto K, Uemura D, Hartshorne DJ.: "Calyculin A and okadaic acid: Inhibitors of protein phosphatase activity." Biochemical and Biophysical Research Communications 159, 871-877, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hartshorne DJ, Ishihara H, Karaki H, Ozaki H, Sato K, Hori M, Watabe S.: "Okadaic acid and calyculin A: Effects on smooth muscle s systems." Advance in Protein Phosphatases. 5, 219-231, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Karaki H, Mitsui M, Nagase H, Ozaki H, Shibata S, Uemura D.: "Inhibitory effect of a toxin okadaic acid isolated from the black sponge on smooth muscle and platelets." British Journal of Pharmacology 98, 590-596, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishihara H, Ozaki H, Sato K, Hori M, Karaki H, Watabe S, Kato Y, Fusetani N, Hashimoto K, Uemura D, Hartshorne DJ.: "Calcium-independent activation of contractile apparatus in smooth muscle by calyculin A." Journal of Pharmacology and Experimental Therapeutics. 250, 388-396, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ozaki H,Ishihara H,Kohama K,Nonomura Y,shibata S,Karaki H: "Calcium-indepeudent phosphorylation of smooth muscle myosin light chain by okadaic acid isolated from black sponye" Journal of pharmacology and Experiweutal Therapeutics. 243. 1167-1173 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ishihara H,Martin BL,Braughfigan DL,Karaki H,ozaki H,Kato Y,Fusetani N,watabe S,Hasimoto K,Uemura D,: "Calyculin A and okadaic acid:Inhibitors of protein phosphatase activity." Hartshorne DJ.Biochemical amd Bioplysical Research Communica tions. 159. 871-877 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hartshorne DJ,Ishihara H Karaki H,Ozaki H,Sato K,Hori M,Watabe S.: "Okadaic acid and calyculin A:Effects on Smooth muscle systems." Advauce in protein phosphatases. 5. 219-231 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Karaki H,mitsui M,Nagase H,Ozaki H,Shibata S,Uemura D,: "Iuhibitory elfect of a toxin okadaic acid isolated from the black sponge on smooth musale and platelets" British Journal of pharmacology. 98. 590-596 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Ishihara H,Ozaki H,Sato K,Hori M,Karaki H,Watabe S,Kato Y,Fusetani N,Hashimoto K,: "Calcium-independent aceivaeion Ω contraceile apparatus in smooth muscle by calyculin A" Uemura D and Hart shorne DJ.Jourual of Pharmacology and Experimeutal Therapputics. 250. 388-396 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 柴田章次、児玉逸雄、唐木英明: "Okadaic acid の平滑筋および心筋への作用" 実験医学. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Ishihara: Biophys,Biochem.Res.Comm.

    • Related Report
      1988 Annual Research Report
  • [Publications] H.Ishihara: J.Pharmacol.Exp.Ther.

    • Related Report
      1988 Annual Research Report
  • [Publications] H.Karaki: Br.J.Pharmacol.

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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