Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Curr Drug Metab. 2011 Oct;12(8):732-41. doi: 10.2174/138920011798357024.
The recent identification of drug-metabolizing enzymes cytochrome P450 (CYP) in the human blood-brain barrier (BBB) raises the question of whether these enzymes act in concert with ATP-binding cassette (ABC) transporters to limit the brain distributions of drugs. We recently demonstrated several CYP genes in freshly isolated human brain microvessels; the main isoforms expressed were CYP1B1 and CYP2U1. Many studies using different experimental approaches have revealed that P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and the multidrug resistance-associated protein 4 (MRP4, ABCC4) are the main ABC transporters in the human BBB. The first part of this review covers recent studies on the expression, regulation and function of CYP450 and ABC transporters in the rodent and human BBBs. The second part focuses on the possible interplay between some CYPs and certain ABC transporters at the BBB, which makes it a determining element of brain drug concentrations and thus of the effects of centrally acting drugs.
最近在人体血脑屏障（BBB）中发现了细胞色素 P450（CYP）等药物代谢酶，这引发了一个问题，即这些酶是否与 ATP 结合盒（ABC）转运蛋白协同作用，限制药物在大脑中的分布。我们最近在新鲜分离的人脑微血管中鉴定了几种 CYP 基因；表达的主要同工酶是 CYP1B1 和 CYP2U1。许多使用不同实验方法的研究表明，P-糖蛋白（P-gp，ABCB1）、乳腺癌耐药蛋白（BCRP，ABCG2）和多药耐药相关蛋白 4（MRP4，ABCC4）是人体 BBB 中的主要 ABC 转运蛋白。这篇综述的第一部分涵盖了最近关于 CYP450 和 ABC 转运蛋白在啮齿动物和人体 BBB 中的表达、调节和功能的研究。第二部分重点介绍了 BBB 中某些 CYP 和某些 ABC 转运蛋白之间可能的相互作用，这使其成为脑内药物浓度的决定因素，从而影响中枢作用药物的效果。
