The cerebrospinal fluid-to-blood efflux transport of estrone-3-sulfate (E1S) via the blood-cerebrospinal fluid barrier (BCSFB) may play an important role in regulating E1S levels in the brain. Here, we investigated the efflux transport of E1S at the BCSFB using conditionally immortalized rat choroid plexus epithelial cells (TR-CSFB) and identified the responsible transporter. The [3H]E1S uptake by TR-CSFB cells was composed of saturable and nonsaturable components, and the Km and Vmax values of the saturable component were determined to be 16.8 ± 5.1 μM and 12.3 ± 2.3 pmol/min/mg of protein, respectively. [3H]E1S uptake was inhibited by probenecid, cholate, taurocholate, sulfobromophthalein, dehydroepiandrosterone sulfate, triiodothyronine, thyroxin, and digoxin but not by p-aminohippuric acid, γ-aminobutyric acid, or methotrexate, suggesting the involvement of organic anion transporting polypeptide (oatp) in the uptake. Reverse transcription-polymerase chain reaction analysis revealed that oatp3 was expressed in TR-CSFB cells and isolated rat choroid plexus, although oatp1 was not detected in either. Xenopus laevis oocytes expressing oatp3 exhibited [3H]E1S uptake activity with a Km of 8.09 ± 2.83 ±M and Vmax of 8.02 ± 0.87 pmol/h/oocyte. Moreover, oatp3 is localized at the brush-border membrane of choroid plexus epithelial cells. These results suggest that oatp3 is involved in the E1S efflux transport at the BCSFB.
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