Quantitative atlas of blood-brain barrier transporters, receptors, and tight junction proteins in rats and common marmoset

Yutaro Hoshi, Yasuo Uchida, Masanori Tachikawa, Takashi Inoue, Sumio Ohtsuki, Tetsuya Terasaki

研究成果: Article査読

132 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3343-3355
ページ数13
ジャーナルJournal of Pharmaceutical Sciences
102
9
DOI
出版ステータスPublished - 2013 9

ASJC Scopus subject areas

  • Pharmaceutical Science

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