Comparison of Absolute Protein Abundances of Transporters and Receptors among Blood-Brain Barriers at Different Cerebral Regions and the Blood-Spinal Cord Barrier in Humans and Rats

Yasuo Uchida, Yuta Yagi, Masaki Takao, Masaki Takao, Mitsutoshi Tano, Mina Umetsu, Satoshi Hirano, Takuya Usui, Masanori Tachikawa, Tetsuya Terasaki

Research output: Contribution to journalArticlepeer-review

Abstract

This work was designed to clarify the absolute abundances of transporters and receptors at different cerebral regions of the blood-brain barriers (BBB) and blood-spinal cord barrier (BSCB) in humans and rats, using physiologically relevant units (pmol/g tissue and fmol/cm2); 39 and 29 proteins including tight-junction proteins and markers were quantified in human and rat capillary samples, respectively. Protein expression levels of almost all proteins were identical within a 2-fold range between BBB and BSCB in rats, while many proteins showed >2-fold smaller expression levels in BSCB than BBB in humans. Protein expression levels of transporters and receptors in humans were remarkably smaller than those in rats in both BBB and BSCB in units of pmol/g tissue and fmol/cm2. Protein expression levels (fmol/cm2) of MDR1 and BCRP at the BBB in humans were 9.88-fold and 5.23-fold smaller than those in rats, respectively. GLUT1 expression (pmol/g tissue) at cortical BBB in a human was 2.49- and 3.76-fold greater than that at white matter BBB and BSCB, respectively. INSR and LRP1 proteins were detected at cortical BBB, but not at white matter BBB or BSCB in humans. These findings throw light on regional differences and species differences in pharmacokinetics and physiological functions in the central nervous system.

Original languageEnglish
Pages (from-to)2006-2020
Number of pages15
JournalMolecular pharmaceutics
Volume17
Issue number6
DOIs
Publication statusPublished - 2020 Jun 1

Keywords

  • blood-brain barrier (BBB)
  • blood-spinal cord barrier (BSCB)
  • fmol/cm
  • pmol/g tissue
  • species difference

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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