title: Novel plasma membrane action of estrogen and antiestrogens revealed by their regulation of a large conductance chloride channel.
abstract: Antiestrogens antagonize many genomic effects of estrogen through binding to the nuclear estrogen receptor. We report here that NIH3T3 fibroblasts grown in the presence of colchicine acquire the activation of a large conductance chloride channel upon exposure to extracellular but not intracellular antiestrogens. This effect can be prevented by extracellular 17 beta-estradiol, but not intracellular 17 beta-estradiol or extracellular 17 alpha-estradiol. This is the first demonstration of a regulatory role for antiestrogens and estrogens in the regulation of ionic channels occurring through an interaction of these compounds with a plasma membrane binding site distinct from the classical estrogen receptor and subsequent activation of intracellular second messenger pathway (or pathways).
authors.affiliation: AFRC Babraham Institute, Cambridge, United Kingdom.
authors.forename: S P
authors.initials: SP
authors.lastname: Hardy
authors.forename: M A
authors.initials: MA
authors.lastname: Valverde
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D003078:Colchicine; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D017312:Toremifene / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D004958:Estradiol; D017312:Toremifene; D003078:Colchicine