NOVEL PLASMA-MEMBRANE ACTION OF ESTROGEN AND ANTIESTROGENS REVEALED BY THEIR REGULATION OF A LARGE-CONDUCTANCE CHLORIDE CHANNEL

Antiestrogens antagonize many genomic effects of estrogen through bind ing to the nuclear estrogen receptor. We report here that NIH3T3 fibro blasts 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 extr acellular 17 beta-estradiol, but not intracellular l7 beta-estradiol o r extracellular 17 alpha-estradiol. This is the first demonstration of a regulatory role for antiestrogens and estrogens in the regulation o f ionic channels occurring through an interaction of these compounds w ith a plasma membrane binding site distinct from the classical estroge n receptor and subsequent activation of intracellular second messenger pathway (or pathways).