Kusuhara Hiroyuki, Sugiyama Yuichi
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
NeuroRx. 2005 Jan;2(1):73-85. doi: 10.1602/neurorx.2.1.73.
The brain uptake of xenobiotics is restricted by the blood-brain brain barrier formed by brain capillary endothelial cells. Active efflux transport systems in the blood-brain barrier work as a detoxification system in the brain by facilitating removal of xenobiotic compounds from the brain. Drugs, acting in the brain, have to overcome such efflux mechanisms to achieve clinically significant concentration in the brain. Multiple transporters are involved in this efflux transport in the brain capillaries. In the past few years, considerable progress has been made in the cloning of these transporters and their functional characterization after heterologous expression. Members of the solute carrier family (SLC) play an important role in the efflux transport, especially for organic anions, which include organic anion transporting polypeptides (OATP/SLCO) and organic anion transporters (OAT/SLC22A). It is believed that coordination of the members of SLC family, and ABC transporters, such as P-glycoprotein, multidrug resistance protein, and breast cancer-resistant protein (BCRP/ABCG2), allows an efficient vectorial transport across the endothelial cells to remove xenobiotics from the brain. In this review, we shall summarize our current knowledge about their localization, molecular and functional characteristics, and substrate and inhibitor specificity.
外源性物质的脑摄取受到脑毛细血管内皮细胞形成的血脑屏障的限制。血脑屏障中的主动外排转运系统通过促进外源性化合物从脑中清除，起到脑内解毒系统的作用。作用于脑内的药物必须克服这种外排机制，才能在脑中达到具有临床意义的浓度。多种转运体参与脑毛细血管中的这种外排转运。在过去几年中，这些转运体的克隆及其在异源表达后的功能表征取得了相当大的进展。溶质载体家族（SLC）成员在这种外排转运中发挥重要作用，特别是对于有机阴离子，其中包括有机阴离子转运多肽（OATP/SLCO）和有机阴离子转运体（OAT/SLC22A）。据信，SLC家族成员与ABC转运体（如P-糖蛋白、多药耐药蛋白和乳腺癌耐药蛋白（BCRP/ABCG2））的协同作用，能够实现跨内皮细胞的高效矢量转运，从而将外源性物质从脑中清除。在这篇综述中，我们将总结目前关于它们的定位、分子和功能特性以及底物和抑制剂特异性的知识。
