Ho M M, Scales D J, Inesi G
Biochim Biophys Acta. 1983 Apr 21;730(1):64-70. doi: 10.1016/0005-2736(83)90317-6.
The inhibitory effect of trifluoroperazine (25-200 microM) on the sarcoplasmic reticulum calcium pump was studied in sarcoplasmic reticulum vesicles isolated from skeletal muscle. It was found that the lowest effective concentrations of trifluoroperazine (10 microM) displaces the Ca2+ dependence of sarcoplasmic reticulum ATPase to higher Ca2+ concentrations. Higher trifluoroperazine concentrations (100 microM) inhibit the enzyme even at saturating Ca2+. If trifluoroperazine is added to vesicles filled with calcium in the presence of ATP, inhibition of the catalytic cycle is accompanied by rapid release of accumulated calcium. ATPase inhibition and calcium release are produced by identical concentrations of trifluoroperazine and, most likely, by the same enzyme perturbation. These effects are related to partition of trifluoroperazine ino the sarcoplasmic reticulum membrane, and consequent alteration of the enzyme assembly within the membrane structure, and of the bilayer surface properties. The effect of trifluoroperazine was also studied on dissociated ('chemically skinned') cardiac cells undergoing phasic contractile activity which is totally dependent on calcium uptake and release by sarcoplasmic reticulum, and is not influenced by inhibitors of slow calcium channels. It was found that trifluoroperazine interferes with calcium transport by sarcoplasmic reticulum in situ, as well as with the role of sarcoplasmic reticulum in contractile activation.
在从骨骼肌分离的肌浆网囊泡中研究了三氟拉嗪（25 - 200微摩尔）对肌浆网钙泵的抑制作用。发现三氟拉嗪的最低有效浓度（10微摩尔）使肌浆网ATP酶对钙离子的依赖性向更高钙离子浓度偏移。更高浓度的三氟拉嗪（100微摩尔）即使在钙离子饱和时也会抑制该酶。如果在ATP存在的情况下将三氟拉嗪添加到充满钙离子的囊泡中，催化循环的抑制会伴随着积累的钙离子的快速释放。ATP酶抑制和钙离子释放是由相同浓度的三氟拉嗪产生的，很可能是由相同的酶扰动引起的。这些效应与三氟拉嗪在肌浆网膜中的分配有关，进而与膜结构内酶组装以及双层表面性质的改变有关。还研究了三氟拉嗪对进行阶段性收缩活动的解离（“化学去表皮”）心肌细胞的影响，这种收缩活动完全依赖于肌浆网对钙的摄取和释放，且不受慢钙通道抑制剂的影响。发现三氟拉嗪会干扰原位肌浆网的钙转运以及肌浆网在收缩激活中的作用。
