Effects of NA0344, a new smooth muscle relaxant, on the actin-myosin-ATP interaction and myosin light chain phosphorylation in vitro.
1. Effects of antibiotic NA0344, a smooth muscle relaxant, on phosphorylation of myosin light chain (MLC, 20 kDa) were compared with those on actin-myosin-ATP interaction using native actomyosin preparation containing MLC kinase activity. 2. MLC kinase was shown to be the site of action of NA0344. 3. NA0344 inhibited the interaction and phosphorylation with IC50 = 7.5 x 10(-6) and 1.6 x 10(-5) M, respectively. 4. The discrepancy between the inhibitory effects is explained that myosin is in an active form when myosin is fully phosphorylated. 5. However, the inhibitory effects of NA0359 and NA0362, analogs of NA0344, on the phosphorylation were similar to or more effective than those on the interaction, which cannot be explained by the active form hypothesis. 6. Plausible explanations for the discrepancies are discussed.
Kohama
K
K
Department of Pharmacology, Gunma University School of Medicine, Maebashi, Japan.
Hiramura
T
T
Takano-Ohmuro
H
H
Ozaki
H
H
Karaki
H
H
Hachisu
M
M
D000199:Actins / Q000494:pharmacology*; D000205:Actomyosin / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003720:Densitometry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009218:Myosins / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation
D000199:Actins; D002227:Carbazoles; D007211:Indoles; D009124:Muscle Proteins; C059549:NA 0344; C070248:NA 0362; C070247:NA 0359; D000255:Adenosine Triphosphate; D000205:Actomyosin; D009219:Myosin-Light-Chain Kinase; D009218:Myosins