The xenoestrogens ethinylestradiol and bisphenol A regulate BCRP at the blood-brain barrier of rats

• Verfasst von: Nickel, Sabrina [VerfasserIn]
• Verfasst von: Mahringer, Anne [VerfasserIn]
• Titel: The xenoestrogens ethinylestradiol and bisphenol A regulate BCRP at the blood-brain barrier of rats
• Verf.angabe: Sabrina Nickel, Anne Mahringer
• E-Jahr: 2014
• Jahr: 19 Jun 2014
• Umfang: 9 S.
• Teil: volume:44
• Teil: year:2014
• Teil: number:11
• Teil: pages:1046-1054
• Teil: extent:9
• Fussnoten: Gesehen am 09.04.2021
• Titel Quelle: Enthalten in: Xenobiotica
• Ort Quelle: Abingdon : Taylor & Francis Group, 1971
• Jahr Quelle: 2014
• Band/Heft Quelle: 44(2014), 11, Seite 1046-1054
• ISSN Quelle: 1366-5928
• DOI: doi:10.3109/00498254.2014.922226
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 17α-Ethinylestradiol
• Sach-SW: bisphenol A
• Sach-SW: blood-brain barrier
• Sach-SW: breast cancer resistance protein
• Sach-SW: xenoestrogen
• K10plus-PPN: 1753563259

Abstract

1. Breast cancer resistance protein (BCRP) is an ABC-transporter at the blood-brain barrier (BBB) facilitating efflux of xenobiotics into blood. Expression and function are regulated via estrogen-receptors (ERs).2. 17α-Ethinylestradiol (EE2) and bisphenol A (BPA) represent two prominent xenoestrogens. We studied whether EE2 and BPA regulate BCRP function and expression upon a 6 h treatment in an ER-dependent manner in a rat BBB-ex-vivo-model.3. Isolated brain capillaries were incubated with EE2 or BPA. BCRP function and expression were analyzed by confocal microscopy and Western-Blot. ERα-antagonist MPP and ER-antagonist ICI182.780 were used to study involvement of ERs.4. EE2 and BPA down-regulated BCRP transport function and expression. EE2 effects occurred at pharmacologically relevant doses, BPA exhibited only weak influences. Down-regulation by EE2 was reversed by ICI but not MPP. BPA effects were not reversed by either antagonist.5. EE2 is a potent regulator of BCRP expression and function acting by ERβ-stimulation. Oral contraception could alter uptake of pharmaceuticals to the brain and might thus be considered as an origin of central nervous system (CNS) side-effects. EE2 could also present a novel co-treatment to improve CNS-pharmacotherapy. BPA is a weak modulator of BCRP expression. Its effects appear not to be caused by ERs.