Carrier-mediated transport blood-brain barrier

ROLE OF TRANSPORT PROCESSES AT THE BLOOD-BRAIN BARRIER CARRIER-MEDIATED TRANSPORT OF DRUGS... 

Pardridge WM. 1998. Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids. Neurochem. Res. 23 635 14... 

P. Tornquist and A. Aim. Carrier-mediated transport of amino acids through the blood-retinal and the blood-brain barriers. Graefes Arch, Clin. Exp. Ophthalmol. 224 21-25 (1986). 

W. M. Partridge, Carrier mediated transport of thyroid hormones through the rat blood brain barrier. Primary role of albumin bound hormone, J. Clin. Invest. 64 145-154 (1979). 

Takasawa M, Terasaki T, Suzuki H, Sugiyama Y (1997) hi vivo evidence for carrier-mediated efflux transport of 3 azido-3 deoxythymidine and 2 ,3 -dideoxyinosine across the blood- brain barrier via a probenecid-sensitive transport system. J Pharmacol Exp Ther 281 369-375. 

Banks WA, Kastin AJ, Eischman AJ, Coy DH, Strauss SL (1986) Carrier-mediated transport of enkephalins and N-Tyr-MIE-1 across blood-brain barrier. Am J Physiol 25LE477-E482. 

Figure 2 Schematic illustration of the (transport) properties of the blood-brain barrier. Shown is the influence of astrocyte endfeet at the brain capillary endothelial cell. This cell has narrow tight junctions, low pinocytotic activity, many mitochondria, and luminal anionic sites that hinder the transport of negatively charged compounds. Passive hydrophilic transport occurs via paracellular diffusion (tight junctions), whereas passive lipophilic transport is a transcytotic process. Adsorptive-, receptor-, and carrier-mediated transport has been indicated. The metabolic properties of the BBB are illustrated by the various enzymes at the BBB [from (157), with permission].

Mercury is unusual in its ability to induce delayed neurological effects. This is especially prevalent with exposure to alkyl mercury compounds. In such cases, the onset of adverse effects may be delayed for months after the initial exposure. The delayed effects of methyl- and dimethylmercury reported in human poisonings are thought, in part, to result from binding to red blood cells, and subsequent slow release. Methylmercury also forms a complex in plasma with the amino acid cysteine, which is structurally similar to the essential amino acid methionine (Aschner and Clarkson 1988). Clarkson (1995) proposed that methylmercury can cross the blood-brain barrier "disguised" as an amino acid via a carrier-mediated system (i.e., transport is not solely the result of methylmercury s lipid solubility). 

A similarly depressing picture exists with tumours in the brain. Conventional anticancer chemotherapy often cannot penetrate the barrier to attack the tumour. The CNS, however, does require low-molecular-weight molecules to grow and function and these small polar molecules (e.g. amino acids, sugars) have their own transport proteins located at the blood-brain barrier that act to transfer the essential compound through the barrier in a process called carrier-mediated transport. 

Oldendorf, WH, (1973) Carrier-mediated blood—brain barrier transport of short-... 

Na+-independent and also Na+-dependent GSH transport systems have been found in lens epithelium, retinal Muller cells, brain endothehal cells and astrocytes [82-84]. The Na+-dependent transport mediates GSH uptake,whereas the Na+-independent carrier appears to be mainly involved in GSH efflux. It is worth noting that these transport systems allow GSH transport across the blood-brain barrier in vivo [85]. 

Tsuji A (2005) Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems. NeuroRx 2 54—62. 

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