TABLE 1.
Studies of Blood-Brain Barrier Polarity: Examples of Similarities and/or Differences in Abluminal:Luminal Membrane Cerebral Microvasculature (in Vivo)
| Protein | Observation (Reference) |
|---|---|
| Na+-Amino acid transporter | Functions only on the abluminal membrane20 |
| Na+K+ATPase; 5′ nucleotidase | Both found only on abluminal membrane, whereas alkaline phosphatase and g-glutamyl transpeptidase were present on luminal and abluminal membranes21 |
| γ-Glutamyl transpeptidase | γ-GTP was enriched on the luminal membrane22 |
| Alkaline phosphatase, 5′nucleotidase, thiamine pyrophosphatase | Enriched on luminal membrane in normal mice; but abluminal expression was increased in scrapie infected animals23 |
| Na+/Na+, Na+/H+ transporter | Present on the abluminal, but not luminal membranes24 |
| Mg++ATPase and alkaline phosphatase | In glioblastomas, luminal membrane expression of both markers is increased25 |
| GLUT1 glucose transporter | In normal rats, abluminal membrane GLUT1 is 3-fold greater than luminal membrane26 |
| Transferrin receptor (TfR) | Transcytosis of TfR from luminal to abluminal capillary membrane, and into parenchyma27 |
| P-glycoprotein | P-glycoprotein, responsible for brain efflux of many pharmaceuticals, was highly expressed in luminal capillary membranes28,29 |
| P-glycoprotein | P-glycoprotein activity was in the astrocyte foot process, and not the endothelial cell. In dual label studies P-gp did not colocalize with endothelial GLUT1, but did colocalize with astroglial GFAP30,31 |
| Human GLUT1 glucose transporter | In high-GLUT1-expressing capillaries, the luminal to abluminal membrane ratio <1.0; but >1.0 in low-GLUT1-expressing endothelia2 |
| Monocarboxylic acid transporter (MCT1) | Neonate MCT1 is greater than in adults. Equal MCT1 density in abluminal and luminal membranes at both ages32 |
| Intercellular adhesion molecule-1 (ICAM-1) | In hemangiomas, luminal>abluminal ICAM-1. Age-variations in ICAM expression were seen in mouse BBB33 |
| GLUT1 glucose transporter | Abluminal:luminal ratio is 4:1 in normals; 1:1 in stroke-prone rats34 |
| Ca++ ATPase; Ecto ATPase | Ca++ATPase is luminally enriched, whereas ecto ATPase is primarily localized on abluminal membranes35 |
| Na+/K+ ATPase | Abluminal localization is questioned; lower fixative concentrations produce more luminal membrane labeling36 |
| Essential fatty acid transporters | Hypothesis: essential fatty acids may use lipoprotein receptors on the luminal membrane to enter the CNS37 |
| Neonatal Fc receptor (FcRn) | Abluminal internalization of IgG, and only brain-to-blood transcytosis suggests no luminal FcRn activity38,39 |
| MCT1 | In ketonemic up-regulation, abluminal MCT1 increased 2-fold. Equal abluminal and luminal MCT1 in controls40 |
| Amino acid transporters | Na+-dependent amino acid transporters are abluminal41 |
| Heparin sulfate proteoglycan (HSPG) | Perlecan (a core protein of HSPG) is expressed at the abluminal membrane, where it functions in transport of bFGF42 |
| Rat organic anion transporter 3 (rOAT3) | The acid efflux transporter, rOAT3 is expressed at the abluminal membrane43 |
| Aspartic acid transporter (ASCT2) | ASCT2 immunoreactivity is localized to the abluminal capillary membrane8 |
| Erythropoietin receptor (EPO-r) | EPO-r is equally expressed on luminal and abluminal BBB membranes, as well as astrocytic end feet. Upregulation of EPO-r is seen in epileptogenic hippocampus44 |
| Na+-dependent glucose transporter (SGLT1) | Luminal membrane expression of SGLT1 is suggested45 |