Potent stimulation of myofilament force and ATPase activity of skeletal muscle by eudistomin M, a novel Ca(++)-sensitizing agent from a Caribbean tunicate

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.