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.

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.