期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 56, 期 12, 页码 1741-1763出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2004.07.007
关键词
efflux transport; organic anion; organic cation; OCT; OAT; OATP; MRP
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 rnonolayer. 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 cations. In contrast, the molecular characteristics of basolateral transporters have not been fully elucidated. Mrp1 is involved in the excretion of etoposide at the basolateral membrane of the CPE, but its contribution to the excretion of organic anions, especially amphipathic conjugated metabolites, remains controversial. The present manuscript summarizes the efflux transport mechanisms at the choroid plexus and focuses on the molecular characteristics of these transporters. (C) 2004 Published by Elsevier B.V.
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