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

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3343-3355
Number of pages13
JournalJournal of Pharmaceutical Sciences
Volume102
Issue number9
DOIs
Publication statusPublished - 2013 Sep

Keywords

  • ADME
  • Blood-brain barrier
  • Membrane transporter
  • Multidrug resistance transporters
  • P-glycoprotein
  • Permeability
  • Preclinical pharmacokinetics
  • Proteomics
  • Receptors
  • Tight junction

ASJC Scopus subject areas

  • Pharmaceutical Science

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