Quantitative Atlas of Blood–Brain Barrier Transporters, Receptors, and Tight Junction Proteins in Rats and Common Marmoset

The purpose of this study was to determine the protein amounts of blood–brain barrier (BBB) permeability-related transporters, receptors, and tight junction proteins in Sprague Dawley and Wistar rats and common marmoset, and also to investigate inter-species and inter-strain differences across roden...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2013-09, Vol.102 (9), p.3343-3355
Main Authors: Hoshi, Yutaro, Uchida, Yasuo, Tachikawa, Masanori, Inoue, Takashi, Ohtsuki, Sumio, Terasaki, Tetsuya
Format: Article
Language:English
Subjects:
ADME
Animals
Blood-Brain Barrier - chemistry
blood–brain barrier
Callithrix
Female
Humans
Macaca
Male
Membrane Transport Proteins - analysis
membrane transporter
multidrug resistance transporters
P-glycoprotein
permeability
preclinical pharmacokinetics
Primates
proteomics
Rats
Rats, Sprague-Dawley
Rats, Wistar
receptors
Receptors, Cell Surface - analysis
Species Specificity
Tandem Mass Spectrometry
tight junction
Tight Junction Proteins - analysis
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Summary:The purpose of this study was to determine the protein amounts of blood–brain barrier (BBB) permeability-related transporters, receptors, and tight junction proteins in Sprague Dawley and Wistar rats and common marmoset, and also to investigate inter-species and inter-strain differences across rodents and primates. Quantification of target proteins in isolated brain capillaries was conducted by liquid chromatography–tandem mass spectrometry-based quantitative targeted absolute proteomics, with in silico peptide selection. Most target proteins showed inter-rodent, inter-primate species, and inter-rat strain differences of less than 2-fold. Comparison of rat and human BBB showed that P-glycoprotein, multidrug resistance-associated protein 4, monocarboxylate transporter 1, l-type amino acid transporter, and organic anion transporter 3 exhibited differences of more than two-fold in protein abundance, whereas the amounts of breast cancer resistance protein, glucose transporter 1, and insulin receptor were similar in rat and human. In contrast, the differences between marmoset and human BBB were less than 2-fold for almost all measured proteins. Thus, the molecular basis of BBB functions may be similar in marmoset and human, whereas that of rats shows significant differences. The marmoset may be a good model to access in vivo human BBB permeability characteristics, as an alternative to rat and macaque monkey. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3343–3355, 2013
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23575