Department of Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA.
Pharm Res. 2010 Oct;27(10):2054-62. doi: 10.1007/s11095-010-0162-2. Epub 2010 May 15.
In the last decade, there has been substantial progress in understanding vectorial ligand transport through rodent and human choroid plexus (CP), the locus of the blood-CSF interface. In this Review, we enumerate the experimental data required to establish vectorial transport through CP and describe transporters involved in vectorial transport across CP. We also note how these transporters differ from those at the blood-brain barrier. The ligand (substrate) examples presented are methyltetrahydrofolate, methotrexate, leukotriene C(4), nucleosides, thiamine monophosphate, prostaglandins, and digoxin. Our focus is on more definitive experiments, including animal and human transporter "knock-outs." Finally, we discuss the neurochemical implications of vectorial transport through CP and the clinical implications of transporter polymorphisms and knockouts. Examples include descriptions of how vectorial transport through the CP for several micronutrients (e.g., methyltetrahydrofolate) nourishes the brain and how knowledge of CP vectorial transport can lead to important treatments.
在过去的十年中,人们对通过啮齿动物和人脉络丛(CP)——血脑屏障的交界部位——进行载体配体转运的理解取得了实质性的进展。在这篇综述中,我们列举了确立 CP 中载体转运所需的实验数据,并描述了涉及 CP 中载体转运的转运体。我们还注意到这些转运体与血脑屏障中的转运体有何不同。所呈现的配体(底物)的例子有:甲基四氢叶酸、甲氨蝶呤、白三烯 C(4)、核苷、硫胺素单磷酸盐、前列腺素和地高辛。我们的重点是更明确的实验,包括动物和人转运体“敲除”。最后,我们讨论了 CP 中载体转运的神经化学意义,以及转运体多态性和敲除的临床意义。例子包括描述 CP 对几种微量营养素(如甲基四氢叶酸)的载体转运如何滋养大脑,以及对 CP 载体转运的了解如何导致重要的治疗方法。