Nongenomic Stimulation of Nitric Oxide Release by Estrogen Is Mediated by Estrogen Receptor α Localized in Caveolae

摘要: Abstract Acute administration of 17β-estradiol (E 2 ) exerts antiatherosclerotic effects in healthy postmenopausal women. The vasoprotective action E may be partly accounted for by a rapid increase nitric oxide (NO) levels endothelial cells (ECs). However, the signaling mechanisms producing this rise are unknown. In an attempt to address short-term effect on NO production, confluent bovine aortic (BAECs) were incubated absence or presence , and production was measured. Significant increases detected after only 5 min exposure without change protein synthase (eNOS). This estrogen significantly blunted various ligands which decrease intracellular Ca 2+ concentration. Furthermore, plasma membrane-impermeable BSA-conjugated BSA) stimulated release, indicating that current system site is membrane rather than classical nuclear receptor. partial antagonist tamoxifen did not block -induced production; however, pure receptor α (ERα) ICI 182,780 completely inhibited -stimulated release. binding confirmed using FITC-labeled BSA BSA-FITC). Western blot analysis showed plasmalemmal caveolae possess ERα addition well-known caveolae-associated proteins eNOS caveolin. study demonstrates nongenomic release -dependent occurs via localized caveolae.