TY - JOUR T1 - Diethylstilbestrol Is a Potent Inhibitor of Store-Operated Channels and Capacitative Ca<sup>2+</sup> Influx JF - Molecular Pharmacology JO - Mol Pharmacol SP - 702 LP - 707 VL - 66 IS - 3 AU - Sergey I. Zakharov AU - Tarik Smani AU - Yuliya Dobrydneva AU - Francisco Monje AU - Craig Fichandler AU - Peter F. Blackmore AU - Victoria M. Bolotina Y1 - 2004/09/01 UR - http://molpharm.aspetjournals.org/content/66/3/702.abstract N2 - We have recently found that diethylstilbestrol (DES), a synthetic estrogen agonist, inhibits thrombin-induced Ca2+ influx in human platelets, but it remains unclear to what extend this effect might be related to the store-operated Ca2+ influx pathway. To study the effect of DES on store-operated channels and capacitative Ca2+ influx, we used rat basophilic leukemia (RBL) cells, vascular smooth muscle cells (SMC), and human platelets, and recorded whole-cell Ca2+ release-activated Ca2+ (CRAC) currents and thapsigargin (TG)-induced capacitative Ca2+ influx. In this study, we demonstrate that extracellular DES produces a dose-dependent and reversible inhibition of CRAC currents in RBL cells (IC50, ∼0.5 μM), whereas intracellular DES (25 μM) has no effect. Extracellular DES (up to 30 μM) inhibited only CRAC but did not affect a whole-cell monovalent cation current mediated by TRPM7 channels. DES effectively inhibited TG-induced capacitative Ca2+ influx in a dose-dependent manner with an IC50 values of ∼0.1 μM in RBL cells, &lt;0.1 μM in SMC, and ∼1 μM in human platelets. It is noteworthy that trans-stilbene, a close structural analog of DES that lacks hydroxyl and ethyl groups, had no effect on CRAC current and on store-operated Ca2+ influx. Thus, we found DES to be a very effective inhibitor of store-operated channels and Ca2+ influx in a variety of cell types. ER -