Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin.
Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin.
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局部麻醉药、美帕林和普萘洛尔是钙调蛋白的拮抗剂。
DOI：
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发表时间：
1981
影响因子：
11.1
通讯作者：
M. B. Feinstein
中科院分区：
文献类型：
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作者：
M. Volpi;R. Sha’afi;P. Epstein;D. Andrenyak;M. B. Feinstein
局部麻醉剂如地布卡因、QX 572、丁卡因和非那卡因，以及具有局部麻醉剂样性质的其他药物（例如，米帕林、普萘洛尔和SKF 525 A）抑制来自脑和心脏的红细胞Ca 2 +-ATP酶（ATP磷酸水解酶，EC 3.6.1.3）和环核苷酸磷酸二酯酶（3 ′，5 ′-环核苷酸5 ′-核苷酸水解酶，EC 3.1.4.17）的特异性钙调素依赖性刺激。这些酶的基础活动在钙调蛋白的情况下是相对不受局部麻醉药的浓度，强烈抑制钙调蛋白的特异性刺激。增加钙调素，而不是Ca 2+，克服了局部麻醉剂对脑磷酸二酯酶的抑制作用。然而，过量的钙调素不能完全恢复红细胞CA 2+刺激的ATP酶的活性。虽然局麻药的作用机制尚不清楚，但它们抑制125 I标记的钙调素与红细胞膜的结合。钙调蛋白的拮抗作用提供了一种分子机制，可以解释局部麻醉剂对许多Ca 2+依赖性细胞过程的抑制-例如，Ca 2+转运、胞吐、兴奋-收缩偶联、非肌细胞运动和聚集。
Local anesthetics such as dibucaine, QX572, tetracaine, and phenacaine, as well as other drugs with local anesthetic-like properties (e.g., mepacrine, propranolol, and SKF 525A) inhibit the specific calmodulin-dependent stimulation of erythrocyte Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and cyclic nucleotide phosphodiesterases (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) from brain and heart. Basal activities of these enzymes in the absence of calmodulin are relatively unaffected by concentrations of local anesthetics that strongly inhibit the specific stimulation by calmodulin. Increasing calmodulin, but not Ca2+, overcomes the inhibitory action of the local anesthetics on brain phosphodiesterase. However, excess calmodulin does not fully restore activity of erythrocyte CA2+-stimulated ATPase. Although the mechanism(s) by which the local anesthetics act is unclear, they inhibit binding of 125I-labeled calmodulin to the erythrocyte membrane. Antagonism of calmodulin provides a molecular mechanism that may explain the inhibition of many Ca2+-dependent cellular processes by local anesthetics--e.g., Ca2+ transport, exocytosis, excitation-contraction coupling, non-muscle-cell motility, and aggregation.