Polla B, Cappelli V, Canepari M, Zanardi M C, Reggiani C
Institute of Human Physiology, University of Pavia, Italy.
Can J Physiol Pharmacol. 1995 May;73(5):661-4. doi: 10.1139/y95-084.
The aim of this study was to determine (i) whether phosphodiesterase inhibitors influenced ATPase activity of maximally calcium activated cardiac myofibrils and (ii) whether this effect varied in relation to isomyosin composition. Myofibrils were prepared from ventricular myocardium of 2- to 3-month-old rats. ATPase activity was determined at low ionic strength at high (> 7.5) and low (4.4) pCa. Five compounds (amrinone, milrinone, enoximone, piroximone, and rolipram) were examined at concentrations between 10 microM and 1 mM. The results obtained showed that only milrinone and amrinone inhibited ATPase activity; inhibition was dose dependent, and milrinone was more potent than amrinone. To assess whether isomyosin composition might influence the responsiveness of myofibrils to phosphodiesterase inhibitors, the effect of 1 mM milrinone was also determined in myofibrils from hypothyroid rats. According to previous observations hypothyroidism caused an isomyosin shift from V1 to V3 in rat ventricular myocardium. The inhibitory effect of milrinone was lower in myofibrils prepared from hypothyroid rats than in myofibrils from euthyroid rats.
（i）磷酸二酯酶抑制剂是否会影响最大钙激活心肌肌原纤维的ATP酶活性；（ii）这种效应是否因同工肌球蛋白组成而异。从2至3月龄大鼠的心室心肌中制备肌原纤维。在低离子强度下，于高（>7.5）和低（4.4）的pCa值下测定ATP酶活性。对浓度在10微摩尔至1毫摩尔之间的五种化合物（氨力农、米力农、依诺昔酮、吡罗昔酮和咯利普兰）进行了检测。所得结果表明，只有米力农和氨力农抑制ATP酶活性；抑制作用呈剂量依赖性，且米力农比氨力农更有效。为评估同工肌球蛋白组成是否可能影响肌原纤维对磷酸二酯酶抑制剂的反应性，还测定了1毫摩尔米力农对甲状腺功能减退大鼠肌原纤维的作用。根据先前的观察结果，甲状腺功能减退导致大鼠心室心肌中同工肌球蛋白从V1向V3转变。甲状腺功能减退大鼠制备的肌原纤维中，米力农的抑制作用低于甲状腺功能正常大鼠制备的肌原纤维。
