Membrane impermeant antioestrogens discriminate between ligand-and voltage-gated cation channels in NG108-15 cells

Allen, Marcus C, Gale, Pamela A, Hunter, A Christy , Lloyd, Andrew and Hardy, Simon P (2000) Membrane impermeant antioestrogens discriminate between ligand-and voltage-gated cation channels in NG108-15 cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1509 (1-2). pp. 229-236. ISSN 0005-2736

Full content URL: https://doi.org/10.1016/S0005-2736(00)00297-2

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Item Type:Article
Item Status:Live Archive

Abstract

Native 5-HT3 and AChR ligand-gated cation channels can be inhibited (blocked) by the non-steroidal antioestrogen tamoxifen. However, the exact site and mechanism of inhibition by tamoxifen on these channels remain unclear. We have investigated the action of the membrane impermeant quaternary derivative, ethylbromide tamoxifen (EBT), on native ligand-gated 5-HT3 receptor channels and voltage-gated K+ channels in NG108-15 cells using whole cell patch clamp. Extracellular EBT inhibited whole cell cationic currents of 5-HT3 receptors with IC50 of 0.22±0.4 μM (nH=1.05±0.2). The channel block was characterised by voltage independent and use independent behaviour (similar to that of tamoxifen). EBT was unable to inhibit voltage-gated K+ currents in NG108-15 cells. This was in contrast to the inhibition by tamoxifen which, at similar concentrations, accelerated the apparent inactivation of these outward K+ currents. The inhibition of 5-HT3 receptors by a membrane impermeant derivative of tamoxifen supports the view that the binding site for antioestrogens is extracellular and the inhibition is not mediated through genomic/transcriptional activity.

Keywords:5-HT3 receptor, Tamoxifen, Ethylbromide tamoxifen, Potassium current
Divisions:College of Science > School of Pharmacy
ID Code:45453
Deposited On:13 Jul 2021 12:34

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