Spector Reynold, Johanson Conrad
Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Pharm Res. 2006 Nov;23(11):2515-24. doi: 10.1007/s11095-006-9091-5. Epub 2006 Oct 18.
With application of molecular biology techniques, there has been rapid progress in understanding how many drugs and micronutrients (e.g., vitamins) are transferred across the choroid plexus (CP), the main transport locus of the blood-cerebrospinal fluid (CSF) barrier, and the renal tubular epithelial cells. In many cases, these molecules are transported by separate, specific carriers or receptors on the apical and/or basal side of the CP or renal epithelial cells. This commentary focuses on four micronutrient transport systems in CP (ascorbic acid, folate, inositol, and riboflavin), all of which have been recently cloned, expressed and for which knockout mice models were developed and transporter localization studies performed. Also reviewed is the recently cloned uric acid transport system in human kidney in which there exists a human "knockout" model. The implications of these transport systems for drug therapy of central nervous system and renal disorders are discussed, especially with regard to methods to circumvent the blood-brain and blood-CSF barriers to deliver drugs to the brain.
随着分子生物学技术的应用,在了解多种药物和微量营养素(如维生素)如何通过脉络丛(CP)、血脑脊髓液(CSF)屏障的主要转运位点以及肾小管上皮细胞进行转运方面取得了迅速进展。在许多情况下,这些分子通过CP或肾上皮细胞顶端和/或基底侧的不同特异性载体或受体进行转运。本述评重点关注脉络丛中的四种微量营养素转运系统(抗坏血酸、叶酸、肌醇和核黄素),所有这些转运系统最近均已克隆、表达,并建立了基因敲除小鼠模型并进行了转运体定位研究。还综述了最近在人肾中克隆的尿酸转运系统,其中存在人类“基因敲除”模型。讨论了这些转运系统对中枢神经系统和肾脏疾病药物治疗的影响,特别是关于绕过血脑屏障和血脑脊液屏障将药物递送至脑的方法。