Transepithelial transport of organic anions across the choroid plexus: Possible involvement of organic anion transporter and multidrug resistance-associated protein

Transport characteristics of 17 beta-estradiol 17 beta-D-glucuronide (E(2)1 7 beta G), a dual substrate of the transporters for cellular uptake (organi c anion-transporting polypeptide 1 or oatp1) and cellular excretion (multid rug resistance-associated protein 1or MRP1), in the rat choroid plexus were studied in vivo and in vitro. The uptake of E(2)17 beta G into isolated ch oroid plexus was mediated by an energy-dependent system with a K-m, of 3.4 mu M. Together with the previous finding that oatp1 is localized on the api cal membrane of choroid plexus, these results suggest that oatp1 is respons ible for the uptake of this ligand. After intracerebroventricular administr ation, elimination of E(2)17 beta G from cerebrospinal fluid was probenecid sensitive and much more rapid than that of inulin; less than 2% of the adm inistered E(2)17 beta G and 40 to 50% of inulin remained in the cerebrospin al fluid 20 min after intracerebroventricular administration. In addition, the amount of E(2)17 beta G associated with choroid plexus at 20 min was ne gligible, suggesting the presence of an efficient excretion system on the b asolateral membrane of choroid plexus. Expression of MRP1 was detected in c horoid plexus. Semiquantitative reverse transcription-polymerase chain reac tion and Western blot analyses indicated that the expression level of MRP1 in choroid plexus is about four or five times higher than that in the lung, one of the tissues exhibiting high expression of MRP1. Together with the i n vivo vectorial transport of E(2)17 beta G, these results can be accounted for by assuming that there is basolateral localization of MRP1 in choroid plexus. Combined, oatp1 and MRP1 may synergistically mediate the efficient transcellular transport of E(2)17 beta G across choroid plexus.