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.
Ohizumi
Y
Y
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Matsunaga
K
K
Nakatani
K
K
Kobayashi
J
J
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects*; D009218:Myosins / Q000032:analysis; D011817:Rabbits
D002243:Carbolines; C056223:eudistomin M; D000251:Adenosine Triphosphatases; D009218:Myosins; D002118:Calcium