Abstract
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.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Brain / blood supply*
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Brain / metabolism*
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Chromatography, Liquid
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Excitatory Amino Acid Transporter 1 / genetics
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Excitatory Amino Acid Transporter 1 / metabolism
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Excitatory Amino Acid Transporter 2
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Glucose Transporter Type 1 / genetics
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Glucose Transporter Type 1 / metabolism
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Glutamate Plasma Membrane Transport Proteins / genetics
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Glutamate Plasma Membrane Transport Proteins / metabolism
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Glutathione S-Transferase pi / genetics
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Glutathione S-Transferase pi / metabolism
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Humans
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In Vitro Techniques
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Microvessels / metabolism*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Proteomics / methods*
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Tandem Mass Spectrometry
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Transcriptome / genetics
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Transcriptome / physiology
Substances
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ABCA2 protein, human
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ABCB1 protein, human
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ABCG2 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2
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Glucose Transporter Type 1
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Glutamate Plasma Membrane Transport Proteins
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Neoplasm Proteins
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SLC1A2 protein, human
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SLC1A3 protein, human
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SLC2A1 protein, human
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GSTM3 protein, human
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GSTO1 protein, human
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GSTP1 protein, human
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Glutathione S-Transferase pi
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Glutathione Transferase