title: Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchida
authors.forename: Sumio
authors.initials: S
authors.lastname: Ohtsuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katsukura
authors.forename: Chiemi
authors.initials: C
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Junichi
authors.initials: J
authors.lastname: Kamiie
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terasaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface