TAMOXIFEN IS A CALMODULIN ANTAGONIST IN THE ACTIVATION OF CAMP PHOSPHODIESTERASE
TAMOXIFEN IS A CALMODULIN ANTAGONIST IN THE ACTIVATION OF CAMP PHOSPHODIESTERASE
复制标题
DOI：
10.1016/0006-291x(84)91062-3
复制
发表时间：
1984-01-01
影响因子：
3.1
通讯作者：
LAM, HYP
中科院分区：
文献类型：
--
作者：
LAM, HYP
他莫昔芬是一种具有抗肿瘤活性的三苯乙烯类抗雌激素药，其作用机制尚未完全确定。在本文中，我们提出的证据表明，他莫昔芬是一个拮抗剂的钙调素，一个主要的细胞钙受体和钙依赖性调节许多细胞过程。我们的数据表明，他莫昔芬抑制磷酸二酯酶的激活钙调素。这种抑制作用可以通过增加钙调素浓度来克服。动力学分析表明，他莫昔芬是钙调蛋白激活该酶的竞争性抑制剂。推测三苯氧胺对钙调素的拮抗作用可能是其药理作用的机制之一。
The mechanism of action of tamoxifen, a triphenylethylene antiestrogen with antitumor activity, has not been fully established. In this paper, we present evidence that tamoxifen is an antigonist of calmodulin, a major cellular calcium receptor and calcium dependent regulator of many cellular processes. Our data showed that tamoxifen inhibited the activation of phosphodiesterase by calmodulin. This inhibition could be overcome by an increase in calmodulin concentration. Kinetic analysis demonstrated that tamoxifen is a competitive inhibitor of calmodulin in the activation of this enzyme. It could be speculated that the antagonism of calmodulin by tamoxifen may be one of the mechanisms responsible for its pharmacological actions.