title: Inhibition of ligand-gated cation-selective channels by tamoxifen.
abstract: 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.
authors.affiliation: Department of Pharmacy, University of Brighton, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Allen
authors.forename: C
authors.initials: C
authors.lastname: Newland
authors.forename: M A
authors.initials: MA
authors.lastname: Valverde
authors.forename: S P
authors.initials: SP
authors.lastname: Hardy
mesh_terms: D000818:Animals; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006825:Hybridomas; D015640:Ion Channel Gating; D008024:Ligands; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D004965:Estrogen Antagonists; D008024:Ligands; D018733:Nicotinic Antagonists; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D013629:Tamoxifen