Abstract
In the course of our survey of biologically active compounds from natural sources, eudistomins were isolated from a Caribbean tunicateEudistoma olivaceum. In the present experiments, eudistomin M (Eud-M, >10-5 M) caused a concentration-dependent increase in the contractile response of skinned fibers from guinea pig skeletal psoas muscles to Ca++. The superprecipitation and ATPase activity of myosin B from fast skeletal muscles of rabbit back and leg were potentiated by this compound (>10-5 M) in a concentration-dependent manner. In skinned fibers, superprecipitation and the ATPase activity of myosin B, Eud-M shifted the concentration-response curve for Ca++ to the upper direction. Ca++-, K+-EDTA- or Mg++-ATPase was not affected by Eud-M. This compound had no effect on the ATPase activity of actomyosin reconstituted from actin and myosin in the presence or absence of troponin. However, the ATPase activity of actin-myosin-troponin-tropomyosin reconstituted system was increased significantly by Eud-M. These results suggest that Eud-M increases the Ca++ sensitivity of the contractile apparatus in skeletal muscles at least partially mediated through troponin-tropomyosin system and thus enhances the ATPase activity of myosin B and the contractile force of myofilament.
Footnotes
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Send reprint requests to: Dr. Yasushi Ohizumi, Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980, Japan.
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↵1 This work was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. Financial support from The Sagawa Foundation for Promotion of Cancer Research and The Nakatomi Foundation are also acknowledged.
- Abbreviations:
- Eud-M
- eudistomin M
- MBED
- 9-methyl-7-bromoeudistomin D
- SR
- sarcoplasmic reticulum
- EGTA
- ethylene glycol bis (β-aminoethyl ether)-N, N′ -tetraacetic acid
- Ms
- methanesulfonate
- Received September 10, 1997.
- Accepted January 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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