Weiss D J, Gurpide E
Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029.
J Steroid Biochem. 1988 Oct;31(4B):671-6. doi: 10.1016/0022-4731(88)90017-9.
In addition to the effects of estrogens on transcription, mediated by the estrogen receptor, and the antiestrogenic effects of triphenylethylene derivatives resulting from their competitive action at the estrogen receptor level, estrogens and antiestrogens can affect cellular processes though other mechanisms. Estrogens can bind and alter enzymatic activities in membranes isolated from target cells, can influence the activities of purified enzymes and can change cell permeability and polarization under conditions excluding transcriptional effects. Triphenylethylene antiestrogens at micromolar concentrations can affect cholinergic, histaminergic and dopaminergic systems, affect calmodulin action and influence protein kinase C activity. Tamoxifen added to suspension of human endometrial adenocarcinoma cells at concentrations greater than 10 microM both increased phosphoinositide hydrolysis and inhibited the stimulatory effect of carbachol on this system. These effects, however, may represent nonspecific actions of the antiestrogens, shared with the structurally related phenothiazines, on the plasma membrane.
除了雌激素通过雌激素受体介导对转录的影响以及三苯乙烯衍生物在雌激素受体水平的竞争性作用所产生的抗雌激素作用外，雌激素和抗雌激素还可通过其他机制影响细胞过程。雌激素可结合并改变从靶细胞分离的膜中的酶活性，可影响纯化酶的活性，并可在排除转录效应的条件下改变细胞通透性和极化。微摩尔浓度的三苯乙烯抗雌激素可影响胆碱能、组胺能和多巴胺能系统，影响钙调蛋白作用并影响蛋白激酶C活性。当以大于10微摩尔的浓度添加到人类子宫内膜腺癌细胞悬液中时，他莫昔芬既增加了磷酸肌醇水解，又抑制了卡巴胆碱对该系统的刺激作用。然而，这些作用可能代表抗雌激素与结构相关的吩噻嗪类药物共有的对质膜的非特异性作用。
