Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
Xavier Declèves
Neuropsychopharmacologie des addictions (CNRS UMR 8206), Faculté de Pharmacie, Université Paris Descartes, Paris, France
Sumio Ohtsuki
Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
Salah Yousif
Neuropsychopharmacologie des addictions (CNRS UMR 8206), Faculté de Pharmacie, Université Paris Descartes, Paris, France
Sandrine Dauchy
Neuropsychopharmacologie des addictions (CNRS UMR 8206), Faculté de Pharmacie, Université Paris Descartes, Paris, France
Aude Jacob
Neuropsychopharmacologie des addictions (CNRS UMR 8206), Faculté de Pharmacie, Université Paris Descartes, Paris, France
Francine Chassoux
Ste Anne Hospital, Paris, France Département de biologie cellulaire, INSERM U567, Institut Cochin, Paris, France
Catherine Daumas-Duport
Ste Anne Hospital, Paris, France Département de biologie cellulaire, INSERM U567, Institut Cochin, Paris, France
Pierre-Olivier Couraud
Departement de biologie cellulaire, INSERM U567, Institut Cochin, Paris, France
Tetsuya Terasaki
Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
Jean-Michel Scherrmann
Neuropsychopharmacologie des addictions (CNRS UMR 8206), Faculté de Pharmacie, Université Paris Descartes, Paris, France
Preferred Abstract (Original):
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.