INHIBITION OF LIGAND-GATED CATION-SELECTIVE CHANNELS BY TAMOXIFEN

The nonsteroidal antioestrogen tamoxifen has been shown to block a num ber of voltage-gated cation-selective channels but its effect on ligan d-gated cation-selective channels has not been studied. We have invest igated the action of tamoxifen and the related derivative toremifene o n ligand-gated cationic nicotinic acetylcholine and 5-HT3, receptor ch annels. Tamoxifen and toremifene both inhibited cationic currents of a dult-type human muscle nicotinic acetylcholine receptors expressed in Xenopus oocytes with similar IC50 values of 1.2 +/- 0.03 mu M (n(H) = 0.84 +/- 0.02) and 1.2 +/- 0.1 mu M (n(H) = 1.1 +/- 0.1), respectively . Tamoxifen could also block native 5-HT3 receptors in NG108-15 neurob lastoma/glioma hybrid cells with IC50 = 0.81 +/- 0.15 mu M and n(H), o f 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-H T consistent with a noncompetitive mechanism of block. (C) 1998 Elsevi er Science B.V. All rights reserved.