Allen M C, Newland C, Valverde M A, Hardy S P
Department of Pharmacy, University of Brighton, UK.
Eur J Pharmacol. 1998 Aug 7;354(2-3):261-9. doi: 10.1016/s0014-2999(98)00454-3.
The nonsteroidal antioestrogen tamoxifen has been shown to block a number of voltage-gated cation-selective channels but its effect on ligand-gated cation-selective channels has not been studied. We have investigated the action of tamoxifen and the related derivative toremifene on ligand-gated cationic nicotinic acetylcholine and 5-HT3 receptor channels. Tamoxifen and toremifene both inhibited cationic currents of adult-type human muscle nicotinic acetylcholine receptors expressed in Xenopus oocytes with similar IC50 values of 1.2 +/- 0.03 microM (nH = 0.84 +/- 0.02) and 1.2 +/- 0.1 microM (nH = 1.1 +/- 0.1), respectively. Tamoxifen could also block native 5-HT3 receptors in NG108-15 neuroblastoma/glioma hybrid cells with IC50 = 0.81 +/- 0.15 microM and nH of 1.3 +/- 0.3. The characteristics of block by tamoxifen at the 5-HT3 receptor were voltage- and use-independent. The inhibition of the 5-HT-evoked currents were not overcome by increasing concentrations of 5-HT consistent with a noncompetitive mechanism of block.
非甾体类抗雌激素他莫昔芬已被证明可阻断多种电压门控阳离子选择性通道，但其对配体门控阳离子选择性通道的作用尚未得到研究。我们研究了他莫昔芬及其相关衍生物托瑞米芬对配体门控阳离子型烟碱型乙酰胆碱和5-HT3受体通道的作用。他莫昔芬和托瑞米芬均抑制非洲爪蟾卵母细胞中表达的成人型人肌肉烟碱型乙酰胆碱受体的阳离子电流，其IC50值相似，分别为1.2±0.03 microM（nH = 0.84±0.02）和1.2±0.1 microM（nH = 1.1±0.1）。他莫昔芬还可阻断NG108-15神经母细胞瘤/胶质瘤杂交细胞中的天然5-HT3受体，IC50 = 0.81±0.15 microM，nH为1.3±0.3。他莫昔芬对5-HT3受体的阻断特性与电压和使用无关。增加5-HT浓度不能克服对5-HT诱发电流的抑制作用，这与非竞争性阻断机制一致。
