Pang D C, Briggs F N
Recent Adv Stud Cardiac Struct Metab. 1975;7:421-4.
Although chlorpromazine and quinidine have dissimilar chemical properties, both are negative inotropic agents and both depress the ATPase activity of cardiac sarcotubular fractions. With the aid of gamma-AT32 P we have identified the step in ATP hydrolysis which is inhibited by each of these agents. By optimizing the conditions for formation of a phosphorylated intermediate (EP) by addition of 5 mM calcium to the incubation medium we found that chlorpromazine (0.25--1 mM) severely depressed EP formation, whereas quinidine (0.25--1 mM) had no effect. After the isolation of EP we showed that chlorpromazine had no effect on the magnesium-facilitated hydrolysis of EP, whereas quinidine was a potent inhibitor of this hydrolytic step. The effects of both quinidine and chlorpromazine on the E + ATP equilibrium EP + ADP reaction were studied. Quinidine had no effect on this reaction, whereas chlorpromazine, at 1 mM, shifted the reaction toward ATP formation.
尽管氯丙嗪和奎尼丁具有不同的化学性质，但二者均为负性肌力药物，且都能抑制心肌肌管部分的ATP酶活性。借助γ-AT32 P，我们确定了ATP水解过程中被这两种药物各自抑制的步骤。通过向孵育培养基中添加5 mM钙来优化磷酸化中间体（EP）形成的条件，我们发现氯丙嗪（0.25 - 1 mM）严重抑制EP的形成，而奎尼丁（0.25 - 1 mM）则无此作用。在分离出EP后，我们发现氯丙嗪对镁促进的EP水解没有影响，而奎尼丁是该水解步骤的有效抑制剂。研究了奎尼丁和氯丙嗪对E + ATP平衡反应EP + ADP的影响。奎尼丁对该反应无影响，而1 mM的氯丙嗪则使反应向ATP生成方向移动。
