Influence of isoproterenol and calcium on cadmium- or lead-induced negative inotropy related to cardiac myofibrillar protein phosphorylations in perfused rat heart.
Influence of isoproterenol and calcium on cadmium- or lead-induced negative inotropy related to cardiac myofibrillar protein phosphorylations in perfused rat heart.
复制标题
异丙肾上腺素和钙对镉或铅诱导的与灌注大鼠心脏中心肌原纤维蛋白磷酸化相关的负性肌力的影响。
DOI：
10.1016/0041-008x(80)90214-8
复制
发表时间：
1980
影响因子：
3.8
通讯作者：
Michael Bárány
中科院分区：
文献类型：
--
作者：
Stephen J. Kopp;Michael Bárány
负性肌力药物镉的单独和组合生理和肌原纤维蛋白磷酸化作用（3 × 10− 3 mm）和铅（3 × 10− 4毫米），正性肌力药异丙肾上腺素（7 × 10− 7米）和钙（6.5 mm）在离体改良灌注大鼠心脏制备物中进行检查，以评估镉和铅之间可能的因果关系，诱导肌原纤维蛋白磷酸化的变化和变力性反应的改变。镉和铅单独抑制心肌收缩力，仅抑制肌球蛋白轻链-2（LC-2）的磷酸化。这些影响在异丙肾上腺素和细胞外钙升高的存在下减弱;然而，镉和铅抑制了钙和异丙肾上腺素对心脏的正性肌力激活，以及伴随的所谓的心脏调节磷酸化蛋白LC-2和肌钙蛋白抑制亚基（TN-I）磷酸化的增加。对β-肾上腺素能激动剂的正性变时性反应不受镉和铅的影响。这些结果表明，镉和铅的负性肌力作用与抑制LC-2和TN-I的磷酸化有关。此外，目前的研究结果表明，镉和铅可能会改变肌原纤维蛋白磷酸化机制拮抗肌膜钙易位过程，但是，这些结果并不排除直接细胞内拮抗钙依赖的过程，这些重金属离子的可能性。
The individual and combined physiological and myofibrillar protein phosphorylation effects of the negative inotropic agents, cadmium (3 × 10−3mm) and lead (3 × 10−4mm), and the positive inotropic agents isoproterenol (7 × 10−7m) and calcium (6.5 mm) were examined in isolated modified perfused rat heart preparations to evaluate possible causal associations between cadmium- and lead-induced changes in myofibrillar protein phosphorylations and altered inotropic responsiveness. Cadmium and lead alone depressed cardiac contractility and only the phosphorylation of the myosin light chain-2 (LC-2). These effects were attenuated in the presence of isoproterenol and elevated extracellular calcium; however, cadmium and lead inhibited both the positive inotropic activation of the heart by calcium and isoproterenol and the concomitant increase in phosphorylations of the purported cardioregulatory phospho-proteins, LC-2 and the troponin inhibitory subunit (TN-I). Positive chronotropic responses to the β-adrenergic agonist were unaffected by cadmium and lead. These results suggest that the negative inotropic effects of cadmium and lead are related to depressed phosphorylation of LC-2 and TN-I. Furthermore, the present findings suggest that cadmium and lead may alter myofibrillar protein phosphorylation mechanisms by antagonizing sarcolemmal calcium translocation processes; however, these results do not preclude the possibility of direct intracellular antagonisms of calcium-dependent processes by these heavy metal ions.