Vol. 285, Issue 2, 695-699, May 1998

Potent Stimulation of Myofilament Force and ATPase Activity of Skeletal Muscle by Eudistomin M, a Novel Ca⁺⁺-Sensitizing Agent from a Caribbean Tunicate¹

Yasushi Ohizumi, Kimihiro Matsunaga, Keigo Nakatani and Jun'ichi Kobayashi

Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences (Y.O., K.M., K.N.), Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980, Japan and Department of Pharmacognosy, Faculty of Pharmaceutical Sciences (J.K.), Hokkaido University, Sapporo 060, Japan

In the course of our survey of biologically active compounds from natural sources, eudistomins were isolated from a Caribbean tunicate Eudistoma 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.