TY - JOUR T1 - Abundant expression of OCT2, MATE1, OAT1, OAT3, PEPT2, BCRP, MDR1 and xCT transporters in blood-arachnoid barrier of pig, and polarized localizations at CSF- and blood-facing plasma membranes JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.119.089516 SP - dmd.119.089516 AU - Yasuo Uchida AU - Ryohei Goto AU - Hina Takeuchi AU - Magdalena Ɓuczak AU - Takuya Usui AU - Masanori Tachikawa AU - Tetsuya Terasaki Y1 - 2019/01/01 UR - http://dmd.aspetjournals.org/content/early/2019/11/26/dmd.119.089516.abstract N2 - The physiological and pharmacological roles of the blood-arachnoid barrier (BAB) remain unclear. Therefore, the purpose of the present study was to comprehensively evaluate and compare the absolute protein expression levels of transporters in the leptomeninges and in the choroid plexus per cerebrum, and to determine the localizations of transporters at the CSF- and blood (dura)-facing plasma membranes of the BAB in pig. Using MDR1 and OAT1 as blood (dura)-facing and CSF-facing plasma membrane marker proteins, respectively, we established that BCRP, MRP4, OATP2B1, MATE1 and GLUT1 are localized at the blood-facing plasma membrane, and OAT3, PEPT2, MRP3, OCT2, xCT, MCT1, MCT4, MCT8 are localized at the CSF-facing plasma membrane of the BAB. The absolute protein expression levels of OAT1, OAT3, MDR1, BCRP, PEPT2, xCT, MATE1 OCT2 and 4f2hc in the whole BAB surrounding the entire cerebrum were much larger than those in the total of the choroid plexuses forming the blood-cerebrospinal fluid barrier (BCSFB). Although MRP4, OATP2B1, MCT8, GLUT1 and MCT1 were also statistically significantly more abundant in the BAB than in the choroid plexuses per porcine cerebrum, these transporters were nevertheless almost equally distributed between the two barriers. In contrast, OATP1A2, MRP1, OATP3A1 and OCTN2 were specifically expressed in choroid plexus. These results should be helpful to understand the relative overall importance of transport at the BAB compared to that at the BCSFB, as well as the rank order of transport capacities among different transporters at the BAB, and the directions of transport mediated by individual transporters.SIGNIFICANCE STATEMENT We found that BCRP, MRP4, OATP2B1, MATE1 and GLUT1 localize at the blood-facing plasma membrane of the blood-arachnoid barrier (BAB), while OAT3, PEPT2, MRP3, OCT2, xCT, MCT1, MCT4, MCT8 localize at the CSF-facing plasma membrane. 4F2hc is expressed in both membranes. For OAT1, OAT3, MDR1, BCRP, PEPT2, xCT, MATE1 OCT2 and 4f2hc, the absolute protein expression levels in the whole BAB surrounding the entire cerebrum are much greater than the total amounts in the choroid plexuses. ER -