Membrane abluminal

Figure 2 Comparison of intestinal epithelial cells in culture and in situ. (A) Human colon Caco-2 cells grown in culture for 16 days on a semiporous filter. (B) Epithelial layer of rat jejunum. AP, apical or luminal membrane B, basal or abluminal membrane BM, basement membrane G, goblet cell LS, lateral space mv, microvilli Nu, nucleus TJ, tight junction. Bars equal 10 pm. 

Pericytes lie periendothelially on the abluminal side of the microvessels (Figure 15.3). A layer of basement membrane separates the pericytes from the endothelial cells and the astrocyte foot processes. Pericytes send out cell processes which penetrate the basement membrane and cover around 20-30% of the micro-vascular circumference [18]. Pericyte cytoplasmic projections encircling the endothelial cells provide both a vasodynamic capacity and structural support to the microvasculature. They bear receptors for vasoactive mediators such as catecholamines, endothelin-1, VIP, vasopressin and angiotensin II. Pericytes become mark-... 

Lastly, pharmacogenomics could provide new tools for the design of more specific and active CNS pharmaceuticals. The efficacy of a broad spectrum of neuro-pharmaceutical drugs is often complicated by their inability to reach their site of action because of the BBB. One way to overcome this is to use carrier-mediated transport at the luminal and/or abluminal membranes of the endothelial cells of the BBB. This will provide a physiologically based drug delivery strategy for the brain by designing new chemical entities or fused proteins that can cross the BBB via these transporters. 

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 transport of amino acids at the BBB differs depending on their chemical class and the dual function of some amino acids as nutrients and neurotransmitters. Essential large neutral amino acids are shuttled into the brain by facilitated transport via the large neutral amino acid transporter (LAT) system [29] and display rapid equilibration between plasma and brain concentrations on a minute time scale. The LAT-system at the BBB shows a much lower Km for its substrates compared to the analogous L-system of peripheral tissues and its mRNA is highly expressed in brain endothelial cells (100-fold abundance compared to other tissues). Cationic amino acids are taken up into the brain by a different facilitative transporter, designated as the y system, which is present on the luminal and abluminal endothelial membrane. In contrast, active Na -dependent transporters for small neutral amino acids (A-system ASC-system) and cationic amino acids (B° system), appear to be confined to the abluminal surface and may be involved in removal of amino acids from brain extracellular fluid [30]. Carrier-mediated BBB transport includes monocarboxylic acids (pyruvate), amines (choline), nucleosides (adenosine), purine bases (adenine), panthotenate, thiamine, and thyroid hormones (T3), with a representative substrate given in parentheses [31]. 

The process of transcytosis is illustrated in Figure 2.3 for the transferrin receptor (TfR) [37]. The receptor is heavily expressed at the BBB compared to other vascular beds [38]. Transferrin or a monoclonal antibody to the extracellular domain of the receptor protein will bind from the luminal side of the BBB. This triggers cellular uptake by the mechanism of receptor-mediated endocytosis, i.e. the invagination and budding off of parts of the cell membrane as a result of the formation of small vesicles (endosomes). The transceUular passage of ligand (transcytosis) is completed by exocytosis at the abluminal membrane, and the whole process is completed within minutes in vivo. 

The secretion of CSF and ECF is essentially driven by an osmotic gradient created by the Na+/K+-ATPase, expressed in the abluminal membrane of the BBB endothelium and the apical membrane of the choroid plexus epithelium, which produces water movement into brain ECF and produces volume secretion. 

Betz, A.L., J.A. Firth, and G.W. Goldstein. 1980. Polarity of the blood-brain barrier Distribution of enzymes between the luminal and abluminal membranes of brain capillary endothelial cells. Brain Res 192 17. 

Podocytes are polarized cells, so one can differentiate between luminal and abluminal (basal) membrane domains (the basal domain corresponds to the sole plates of the foot processes, which are embedded in the basement membrane). The slit diaphragm forms the border between the luminal and the abluminal membranes. 

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... 

Mori S, Takanaga H, Ohtsuki S, et al. Rat organic anion transporter 3 (iOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab 2003 23 432 140. 

Water moving from the blood into the brain through an intact BBB has to cross three membranes luminal and abluminal endothelial cell membranes, and the membrane of the astrocyte foot processes (Kimelberg, 2004 Tait et al., 2008). High density of AQP4 is present in the vascular-facing astrocytic membranes. Although... 

The mechanism by w hich immunoUposomes penetrate across the BBB is not fully understood. It w as hypothesized that the process involves the binding of immunoliposomes to multiple capillary luminal membrane receptors, fusion of the liposomes with several vesicular pits into a large vesicle and transcytosis of this vesicle to the abluminal membrane border (Comford and Comford, 2002). Studies by electron microscopy support this hypothesis (Faustmann andDermietzel, 1985). 

Capillary Wall (luminal abluminal cell membranes and cytoplasm) 100-150 nm thick... 

Model Plate (Luminal) (abluminal) Membrane Surface ... 

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