Blood-tissue barrier

Polarized tissues directly involved in drug absorption (intestine) or excretion (liver and kidney) and restricted drug disposition (blood-tissue barriers) asymmetrically express a variety of different drug transporters in the apical or basolateral membrane resulting in vectorial dmg transport. This vectorial dmg transport is characterized by two transport processes the uptake into the cell and subsequently the directed elimination out of the cell (Figure 15.3). Because the uptake of substances... 

Fromm, M.F. (2004) Importance of P-glycoprotein at blood-tissue barriers. 

P-gp is constitutively expressed in nearly all barrier tissues. Techniques involving Northern blots (37) or Western blots with monoclonal antibodies such as C219 (38) and MRK 16 (39) have been used extensively to determine the tissue distribution of P-gp. It is expressed in adrenal cortex, kidney, liver, intestine, and pancreas endothelial cells at blood-tissue barriers, namely, the CNS, the testis, and in the papillary dermis (3,4,38,40,41). P-gp displays specific subcellular localization in cells with a polarized excretion or absorption function. More specifically, P-gp is found at the apical (AP) canalicular surface of hepatocytes, in the AP membrane of the columnar epithelial cells of colon and jejunum, and the AP brush border of the renal proximal tubule epithelium (3,4,40 1-2). In endothelial cells, P-gp is located in the luminal membrane (4,43). 

In some instances, P-gp can significantly affect the profile of drug distribution from systemic circulation into organs and tissues, most notably those that possess a specialized blood-tissue barrier such as the brain. Experiments with mdrla(—/—) mice have shown how P-gp affects the distribution of its substrates into certain tissues (11,12,124,212-219). A few examples are shown below to demonstrate the role played by P-gp in the tissue distribution of drugs. 

Other blood-tissue barriers (e.g., blood-thymus, blood-testis) are less well defined [55,56]. An air-blood barrier also has been described that affects the systemic uptake of aerosolized molecules [57]. Therapeutants that target glycoprotein adhesion molecules on endothelium might surmount the blood-brain or other tissue barriers [58]. 

Blood-tissue barrier Transforming growth factor-P2 CD95 Ugand... 

The membrane thickness, h, is a constant at the absorption site but may be altered by disease. Drugs usually diffuse very rapidly into tissues through capillary cell membranes in the vascular compartments. In the brain, the capillaries are densely lined with glial cells creating a thicker lipid barrier (blood-brain barrier) causing a drug to diffuse more slowly into brain. In certain disease states (e.g., meningitis) the cell... 

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