Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier - High affinity transporter for thyroxine

Oatp14/blood-brain barrier-specific anion transporter 1 (Slc21a14) is a novel member of the organic anion transporting polypeptide (Oatp/OATP) family. Northern blot analysis revealed predominant expression of Oatp14 in the brain, and Western blot analysis revealed its expression in the brain capillary and choroid plexus. Immunohistochemical staining indicated that Oatp14 is expressed in the border of the brain capillary endothelial cells. When expressed in human embryonic kidney 293 cells, Oatp14 transports thyroxine (T-4; prothyroid hormone) (K-m = 0.18 muM), as well as amphipathic organic anions such as 17beta estradiol-D-17beta-glucuronide (K-m = 10 muM), cerivastatin (K-m = 1.3 muM), and troglitazone sulfate (K-m = 0.76 muM). The uptake of triiodothyronine (T-3), an active form produced from T-4, was significantly greater in Oatp14-expressed cells than in vector-transfected cells, but the transport activity for T-3 was similar to 6-fold lower that for T-4. The efflux of T-4, preloaded into the cells, from Oatp14-expressed cells was more rapid than that from vector-transfected cells (0.032 versus 0.006 min(-1)). Therefore, Oatp14 can mediate a bidirectional transport of T-4. Sulfobromophthalein, taurocholate, and estrone sulfate were potent inhibitors for Oatp14, whereas digoxin, p-aminohippurate, or leukotriene C-4, or organic cations such as tetraetheylammonium or cimetidine had no effect. The expression levels of Oatp14 mRNA and protein were up- and down-regulated under hypo- and hyperthyroid conditions, respectively. Therefore, it may be speculated that Oatp14 plays a role in maintaining the concentration of T-4 and, ultimately, T-3 in the brain by transporting T-4 from the circulating blood to the brain.