Silver P J, Monteforte P B
Department of Pharmacology, Sterling-Winthrop Research Institute, Rensselaer, NY 12144.
Eur J Pharmacol. 1988 Mar 15;147(3):335-42. doi: 10.1016/0014-2999(88)90166-5.
The effects of four Ca2+ binding protein modulators (bepridil, perhexiline, calmidazolium and trifluoperazine) on cardiac myofibrillar ATPase activity in Triton-purified myofibrils prepared from normal dogs, normal hamsters and age/sex (male, 16-20 weeks)-matched myopathic hamsters (BIO 14.6) have been quantitated. When compared with normal hamsters, myopathic hamster myofibrils have a markedly depressed maximum MgATPase activity (178 +/- 2 vs. 119 +/- 3 nmol/mg per min, respectively) and a slightly increased requirement of Ca2+ for half-maximal activation (ED50; 0.66 vs. 0.75 microM free Ca2+, respectively). Calmidazolium, trifluoperazine and bepridil lower the ED50 for Ca2+ in myopathic myofibrils. Moreover, bepridil and trifluoperazine increase maximum myofibrillar MgATPase activity in myopathic hamster myofibrils. In contrast, calmidazolium depresses maximum and stimulates basal MgATPase activities in myopathic and normal hamster myofibrils. Qualitatively, different effects are apparent when these agents are examined in canine myofibrils. Thus, the pharmacological effects of Ca2+ binding protein modulators on cardiac myofibrillar ATPase activity are dependent upon species and/or pathological state. It is possible to directly enhance a pathological consequence of cardiac myopathy, depression in maximum myofibrillar MgATPase activity, with pharmacological agents.
已经对四种钙离子结合蛋白调节剂（苄普地尔、哌克昔林、氯米帕明和三氟拉嗪）对从正常犬、正常仓鼠以及年龄/性别（雄性，16 - 20周）匹配的患肌病仓鼠（BIO 14.6）制备的经曲拉通纯化的肌原纤维中肌原纤维ATP酶活性的影响进行了定量分析。与正常仓鼠相比，患肌病仓鼠的肌原纤维最大MgATP酶活性显著降低（分别为178±2与119±3 nmol/mg每分钟），并且半最大激活所需的Ca2+量略有增加（ED50；分别为0.66与0.75 μM游离Ca2+）。氯米帕明、三氟拉嗪和苄普地尔降低了患肌病肌原纤维中Ca2+的ED50。此外，苄普地尔和三氟拉嗪增加了患肌病仓鼠肌原纤维中的最大肌原纤维MgATP酶活性。相比之下，氯米帕明降低了患肌病和正常仓鼠肌原纤维中的最大MgATP酶活性并刺激了基础MgATP酶活性。定性地说，当在犬肌原纤维中检查这些药物时，会出现不同的效果。因此，钙离子结合蛋白调节剂对心肌肌原纤维ATP酶活性的药理作用取决于物种和/或病理状态。使用药物有可能直接增强心肌病的一个病理后果，即最大肌原纤维MgATP酶活性降低。
