Efflux transport systems for organic anions and cations at the blood-CSF barrier

Advanced Drug Delivery Reviews
Hiroyuki Kusuhara, Yuichi Sugiyama

Abstract

The choroid plexus (CP), located in the lateral, third and fourth ventricles, is the site of elimination of xenobiotics and endogenous waste from the cerebrospinal fluid (CSF) together with convective flow associated with CSF turnover. Active efflux transport systems, as well as metabolic enzymes in the choroid plexus epithelial cells (CPE), which form a tight monolayer, play a protective role by facilitating the elimination of xenobiotics including drugs and endogenous waste from the CSF to prevent their accumulation in the central nervous system. Except in the case of lipophilic cationic and neutral compounds, uptake and efflux transporters carry out the vectorial transport across the cell monolayer to transfer their common substrates efficiently from the CSF to the blood side. Many published studies have given us some insights into the uptake mechanisms for organic compounds at the brush border side of the CP. Organic anion transporters, such as Oatp3 and Oat3, play a major role in the uptake of amphipathic and hydrophilic organic anions, respectively, at the brush border surface of the CPE, while the organic cation transporters, Oct2 and/or Oct3, have been suggested to be involved in the uptake of hydrophilic organic cation...Continue Reading

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