Ohtsuki Sumio, Hori Satoko, Terasaki Tetsuya
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Nihon Yakurigaku Zasshi. 2003 Jul;122(1):55-64. doi: 10.1254/fpj.122.55.
The blood-brain barrier (BBB) segregates the circulating blood from interstitial fluid in the brain and restricts drug permeability into the brain. Recent studies have revealed that the BBB exhibits not only blood-to-brain influx transport for the supply of nutrients, but also brain-to-blood efflux transport to excrete drugs and endogenous compounds. The influx transport system allows drugs to enter the brain. (L)-DOPA is transported into the brain by the large neutral amino acid transport system, system L. A cationic mu-opioid peptide analogue enters the brain by adsorptive-mediated endocytosis. In contrast, efflux transport limits the distribution of drugs in the brain. The ATP binding cassette transporter B1 (ABCB1) mediates the efflux transport of lipophilic drugs at the BBB by using ATP energy. Furthermore, organic anion transporter 3 (OAT3) is expressed at the BBB and mediates the efflux transport of homovanillic acid, a dopamine metabolite. This efflux transport is also likely to be involved in the transport of anionic drugs such as 6-mercaptopurine and acyclovir. Clarifying the BBB transport could give us important information allowing the development of better CNS drugs and improving our understanding of the relationship between CNS diseases and BBB functions.
血脑屏障（BBB）将循环血液与脑间质液分隔开，并限制药物进入脑内的通透性。最近的研究表明，血脑屏障不仅表现出用于营养物质供应的血脑流入转运，还表现出用于排泄药物和内源性化合物的脑血流出转运。流入转运系统允许药物进入脑内。左旋多巴（L-DOPA）通过大中性氨基酸转运系统L被转运到脑内。一种阳离子μ-阿片肽类似物通过吸附介导的内吞作用进入脑内。相反，流出转运限制了药物在脑内的分布。ATP结合盒转运蛋白B1（ABCB1）利用ATP能量介导血脑屏障处亲脂性药物的流出转运。此外，有机阴离子转运蛋白3（OAT3）在血脑屏障处表达，并介导多巴胺代谢产物高香草酸的流出转运。这种流出转运也可能参与6-巯基嘌呤和阿昔洛韦等阴离子药物的转运。阐明血脑屏障转运可为我们提供重要信息，有助于开发更好的中枢神经系统药物，并增进我们对中枢神经系统疾病与血脑屏障功能之间关系的理解。
