Organic Anion Transporting Polypeptide 2B1 and Breast Cancer Resistance Protein Interact in the Transepithelial Transport of Steroid Sulfates in Human Placenta

• DOI: 10.1124/dmd.106.011411
• Publication Date: 2006-10-05T00:37:19Z
• Authors: Markus Grube; Sebastian Reuther; Henriette Meyer z...; Kathleen Köck; Katrin Draber; Christoph A. Ritter; Christoph Fusch; Gabriele Jedlitschky; Heyo K. Kroemer
• Keywords: Abcg2; Estrone sulfate; Organic anion-transporting polypeptide; Transport protein; Multidrug Resistance-Associated Proteins; Steroid sulfatase

The human placenta has both protective and nurturing functions for the fetal organism. Uptake elimination of xenobiotics endogenous substances are facilitated by various transport proteins from solute carrier (SLC) ABC families, respectively. A functional interaction uptake elimination, which is a prerequisite vectorial across cellular barriers, not been described placenta. In this study, we examined expression organic anion transporter (OAT) 4 (SLC22A11), transporting polypeptide (OATP) 2B1 (SLCO2B1, OATP-B), breast cancer resistance protein (BCRP) (ABCG2) in (<i>n</i> = 71) because all three involved transmembranal transfer estrone 3 sulfate (E3S; metabolic product) dehydroepiandrosterone (DHEAS; precursor molecule). On mRNA level, found significant correlation OATP2B1 BCRP (<i>R</i>² 0.534; <i>p</i> &lt; 0.01) but between OAT4 –0.104; &gt; 0.05). Localization studies confirmed basal apical BCRP. To study interactions BCRP, developed Madin-Darby canine kidney cell model expressing simultaneously (OATP2B1 membrane, respectively). Using transwell system resulted significantly increased to E3S DHEAS, when transporters were expressed with no change direction. Taken together, these data show potential transepithelial steroid sulfates