Neuropsychopharmacologie des addictions (CNRS UMR 8206), Faculté de Pharmacie, Université Paris Descartes, Paris, France.
Mol Pharm. 2011 Aug 1;8(4):1332-41. doi: 10.1021/mp200129p. Epub 2011 Jul 8.
We have investigated the transcriptomic and/or proteomic patterns of 71 solute carrier (SLC) and organic solute (OST) transporters, 34 ATP-binding cassette (ABC) transporters, and 51 metabolizing enzymes in human brain microvessels. We used quantitative RT-PCR and LC-MS/MS to examine isolated brain microvessels and cortex biopsies from 12 patients with epilepsia or glioma. SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels; ABCG2/BCRP was 1.6-fold more expressed than ABCB1/MDR1, and ABCC4/MRP4 was 10 times less abundant than ABCB1/MDR1. CYP1B1 and CYP2U1 were the only quantifiable CYPs. Finally, GSTP1, COMT, GSTM3, GSTO1 and GSTM2 proteins were the main phase II enzymes quantified; UGTs and NATs were not detected. Our extensive investigation of gene and protein patterns of transporters and metabolizing enzymes provides new molecular information for understanding drug entry and metabolism in the human blood-brain barrier.
我们研究了 71 种溶质载体 (SLC) 和有机溶质 (OST) 转运蛋白、34 种 ATP 结合盒 (ABC) 转运蛋白和 51 种代谢酶在人脑微血管中的转录组和/或蛋白质组模式。我们使用定量 RT-PCR 和 LC-MS/MS 检测了 12 名癫痫或脑肿瘤患者的分离脑微血管和皮质活检。SLC2A1/GLUT1、SLC1A3/EAAT1 和 SLC1A2/EAAT2 是主要的 SLC 蛋白，而 ABCG2/BCRP、ABCB1/MDR1、ABCA2 和 ABCA8 是在分离的脑微血管中定量的主要 ABC；ABCG2/BCRP 的表达量是 ABCB1/MDR1 的 1.6 倍，ABCC4/MRP4 的丰度比 ABCB1/MDR1 低 10 倍。CYP1B1 和 CYP2U1 是唯一可定量的 CYP。最后，GSTP1、COMT、GSTM3、GSTO1 和 GSTM2 蛋白是定量的主要 II 期酶；未检测到 UGTs 和 NATs。我们对转运蛋白和代谢酶的基因和蛋白模式进行了广泛的研究，为了解药物进入和代谢提供了新的分子信息人脑血脑屏障。
