新型平滑肌松弛剂NA0344对体外肌动蛋白-肌球蛋白-ATP相互作用及肌球蛋白轻链磷酸化的影响

Effects of NA0344, a new smooth muscle relaxant, on the actin-myosin-ATP interaction and myosin light chain phosphorylation in vitro.

Kohama K, Hiramura T, Takano-Ohmuro H, Ozaki H, Karaki H, Hachisu M

Department of Pharmacology, Gunma University School of Medicine, Maebashi, Japan.

Gen Pharmacol. 1991;22(3):465-74. doi: 10.1016/0306-3623(91)90007-s.

Abstract

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.

摘要

使用含有肌球蛋白轻链激酶活性的天然肌动球蛋白制剂，将平滑肌松弛剂抗生素NA0344对肌球蛋白轻链（MLC，20 kDa）磷酸化的影响与对肌动蛋白 - 肌球蛋白 - ATP相互作用的影响进行了比较。2. 已证明肌球蛋白轻链激酶是NA0344的作用位点。3. NA0344抑制相互作用和磷酸化，IC50分别为7.5×10⁻⁶和1.6×10⁻⁵ M。4. 抑制作用之间的差异解释为当肌球蛋白完全磷酸化时其处于活性形式。5. 然而，NA0344的类似物NA0359和NA0362对磷酸化的抑制作用与对相互作用的抑制作用相似或更有效，这无法用活性形式假说来解释。6. 讨论了对这些差异的合理的解释。