1989 Fiscal Year Final Research Report Summary
Effects of marine toxins on smooth muscle contractile mechanism
| Project/Area Number |
63480088
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
基礎獣医学
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| Research Institution | Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo |
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Principal Investigator |
KARAKI Hideaki Dept of Vet Pharmacol, Fac of Agr, Univ of Tokyo, 農学部, 教授 (60011912)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Smooth Muscle / Contractile proteins / Okadaic acid / Calyculin A / Phosphatase inhibitor |
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| 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.
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[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
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[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
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[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
