Endothelial cells, brain capillary

Fig. 15.3 D iagram showing a longitudinal cross-section of the blood-brain barrier, with the brain capillary endothelial cells sealed by the tight junctions and surrounded by pericytes and astrocyte foot processes. These cellular components of the BBB are separated by a basement membrane.

Fig. 15.5 D iagram showing some of the nutrient and drug transport processes associated with the brain capillary endothelial cells that form the BBB. Local transporters in the luminal or/and abluminal membranes are depicted as filled circles and ones whose location is more questionable or that are present at the BBB are depicted in open circles. GLUT1, LAT1, MCT1, oatp2 are present on both the luminal and abluminal membranes. This diagram shows that transport may be unidirectional or bidirectional.

The presence at the BBB of members of the multidrug resistance-associated protein (MRPs) family, whose members preferentially transport anionic compounds, is still controversial. The seven members of the MRP family belong, like P-gp, to the ATP-binding cassette (ABC) protein superfamily. Mrpl has been found at the BBB in isolated rat brain capillaries, primary cultures of brain capillary endothelial cells and in immortalized capillary endothelial cells, but not in human brain capillaries [59]. Another member, MRP2 has been found at the luminal membrane of the brain endothelial cells [60]. However, further studies are required to show that there are MRP transporters at the BBB (Figure 15.5). As for P-gp, a functional Mrpl was found in primary cultured rat astrocytes [56] and it has been shown to take part in the release of glutathione disulfide from brain astrocytes under oxidative stress [61]. 

The first gene-knockout mouse to become available was a mouse lacking detectable P-gp in the brain capillary endothelial cells. This has been used to elegantly... 

Betz AL, Firth JA, Goldstein GW. Polarity of the blood-brain barrier distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res 1980 192 17-28. 

Brain capillary endothelial cells and some neurons also express a Na+-dependent D-glucose symporter, SGLT1 91... 

Brain capillary endothelial cells and some neurons also express a Na+-dependent D-glucose symporter, SGLT1. SGLT1 (SLC5A1) was the first characterized of the large SLC5 family of Na-dependent symporters (SSSF) which transport various solutes and ions into cells [77, 78]. SGLT1 is found mainly in the intestine, trachea,... 

Zhang, Y., Schuetz, J.D., Elmquist, W.F. and Miller, D.W. (2004) Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells. Journal of Pharmacology and Experimental Therapeutics, 311, 449-455. 

Figure 17.5 Schematic describing the isolation of porcine brain capillary endothelial cells.

Omidi Y, Campbell L, Barar J, Connell D, Akhtar S, Gumbleton M (2003) Evaluation of the immortalised mouse brain capillary endothelial cell line, b.End3, as an in vitro blood-brain barrier model for drug uptake and transport studies. Brain Res 990 95-112... 

Sauer I, et al. An apolipoprotein E-derived peptide mediates uptake of sterically stabilized liposomes into brain capillary endothelial cells. Biochemistry 2005 44 2021. 

Visser, C.C., et al. 2004. Characterisation of the transferrin receptor on brain capillary endothelial cells. Pharm Res 21 761. 

Abbreviations. ( ), there is a discrepancy ND, not determined SLC, solute carrier SM, sinusoidal membrane CM, canalicular membrane BLM, basolateral membrane BBM, brush border membrane LM, luminal membrane ALM, abluminal membrane BBB, brain capillary endothelial cells CPx, choroid plexus. 

Primary cultured porcine or bovine brain capillary endothelial cells have been used as an in vitro model for the BBB. Recently, an immortalized cell line has been established from mouse, rat, and human brain capillary endothelial cells by infection with Simian virus 40 or transfection of SV40 large T antigen (45 -7). Tatsuta et al. established an immortalized mouse brain capillary endothelial cell line (MBEC4). The activity of y-glutamyl transpeptidase and alkaline phosphatase, specific marker enzymes for brain capillary endothelial cells, was half that in the brain capillary (45). Also, P-gp was expressed on the apical membrane of MBEC4 cells, which corresponds to the abluminal membrane of the brain... 

BCRP is classified in ABCG subfamily other members of this subfamily are involved in sterol transport (269). Unlike P-gp and MRPs, BCRP consists of a single ABC cassette in the amino terminal followed by six putative transmembrane domains however, it forms a homodimer linked by a disulfide bond in the plasma membrane (270,271). Initially, ABCG2 was identified as an mRNA expressed in placenta (272) and as a non-MDRl- and non-MRP-type resistance factor from cell lines selected in the presence of anthracy-clines and mitoxantrone (273). BCRP is expressed widely in the normal tissues (274) and localized on the canalicular membrane of the hepatocytes and apical membranes of epithelial cells (274,275) and brain capillary endothelial cells (276,277). 

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