Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors
2011/02/03 by Yasuo Uchida, Sumio Ohtsuki, Yuki Katsukura +4 · 910 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · Neuroscience · #ATP-binding cassette transporter #Abcg2 #Amino Acid Enzymes and Metabolism #Biochemistry #Biology #Blood–brain barrier #Central nervous system #Chemistry #Drug Transport and Resistance Mechanisms #Endocrinology #Gene #Membrane #Membrane protein #Multiple drug resistance #Neuroscience and Neuropharmacology Research #Organic anion transporter 1 #Organic anion-transporting polypeptide #Organic cation transport proteins #P-glycoprotein #Proteomics #Receptor #Transport protein #Transporter
paper · doi:10.1111/j.1471-4159.2011.07208.x
published in Journal of Neurochemistry 117(2), 333-345 (Wiley)
openalex publication_date 2011/02/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
Abstract
We have obtained, for the first time, a quantitative protein expression profile of membrane transporters and receptors in human brain microvessels, that is, the blood-brain barrier (BBB). Brain microvessels were isolated from brain cortexes of seven males (16-77 years old) and protein expression of 114 membrane proteins was determined by means of a liquid chromatography-tandem mass spectrometric quantification method using recently established in-silico peptide selection criteria. Among drug transporters, breast cancer resistance protein showed the most abundant protein expression (8.14 fmol/μg protein), and its expression level was 1.85-fold greater in humans than in mice. By contrast, the expression level of P-glycoprotein in humans (6.06 fmol/μg protein) was 2.33-fold smaller than that of mdr1a in mice. The organic anion transporters reported in rodent BBB, that is, multidrug resistance-associated protein, organic anion transporter and organic anion-transporting polypeptide family members, were under limit of quantification in humans, except multidrug resistance-associated protein 4 (0.195 fmol/μg protein). Among detected transporters and receptors for endogenous substances, the glucose transporter 1 level was similar to that of mouse, while the L-type amino acid transporter 1 level was fivefold smaller than that of mouse. These findings should be useful for understanding human BBB function and its differences from that in mouse.
Citations
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