Organic anion transport across the choroid plexus

Abstract

Several organic anion transport systems have recently been identified and localized at the apical and basolateral plasma membrane domains of choroid plexus epithelial cells. These organic anion transporters include (1) indirectly coupled Na+/dicarboxylate cotransport and dicarboxylate/organic anion exchange, which is represented on the molecular level by a member of the “kidney”‐type organic anion transporter (OAT) family at the apical plasma membrane domain; (2) the organic anion transporting polypeptide 1 (Oatp1) and Oatp2, which both mediate typical “liver”‐like organic anion transport activities at the apical and basolateral plasma membrane domains, respectively; and (3) the multidrug resistance protein Mrp1/MRP1 at the basolateral plasma membrane domain, and the P‐glycoprotein Mdr1/MDR1 at an apical and subapical membrane vesicle compartment. This cellular transport polarity can account, at least in part, for the previously suggested physiologic transport properties of the choroid plexus epithelium and provides a framework for the identification and localization of additional organic anion transporters involved in the absorption and/or excretion of drugs and drug metabolites at the choroid plexus. Microsc. Res. Tech. 52:60–64, 2001. © 2001 Wiley‐Liss, Inc.

How Does the Benzamide Antipsychotic Amisulpride get into the Brain?—An In Vitro Approach Comparing Amisulpride with Clozapine

“…Pgp could also be the reason for the accelerated transport across PCEC, since it was found to be expressed at the luminal side of plexus epithelial cells (Rao et al, 1999). Besides Pgp, multidrug resistance associated protein (MRP2) was detected at the luminal side of PMEC (Miller et al, 2000) and at the basolateral (blood-) side of PCEC (MRP1) (Gao and Meier, 2001). Quite recently, the so-called brain multidrug resistance protein (BMDP), a new member of the ABCG subfamily, was found to be expressed in high rates in PMEC (Eisenblätter and Galla, 2002;Eisenblätter et al, 2003).…”

In Vitro Study of the Functional Expression of Organic Anion Transporting Polypeptide 3 at Rat Choroid Plexus Epithelial Cells and Its Involvement in the Cerebrospinal Fluid-to-Blood Transport of Estrone-3-Sulfate

“…Polarized localization of transporters controls vectorial transport via the BCSFB (Gao and Meier, 2001). oatp3 is localized at the surface of rat choroid plexus epithelial cells (Fig.…”

“…An organic anion transport system at the BCSFB plays a key role in the clearance of endogenous and exogenous anions from the CSF to blood (Forn, 1972;Wong et al, 1993;Suzuki et al, 1997;Gao and Meier, 2001). Two organic anion transporter families have been identified.…”

“…One is the organic anion transporting polypeptide (oatp) family, and the other is the organic anion transporter (OAT) family. At the BCSFB, histochemical studies have shown that oatp1 and OAT3 are localized at the brush-border membrane of choroid plexus epithelial cells (Angeletti et al, 1997;Nagata et al, 2002), and oatp2 is localized at the basolateral membrane (Gao and Meier, 2001). These organic anion transporters transport E 1 S, and therefore it is necessary to investigate the contribution of each transporter to the E 1 S efflux transport at the BCSFB to clarify the efflux mechanism.…”

Impact of Drug Transporter Studies on Drug Discovery and Development

“…Many different drug transporters are expressed in various tissues, such as the epithelial cells of the intestine and kidney, hepatocytes, and brain capillary endothelial cells (Muller and Jansen, 1997;Koepsell, 1998;Meijer et al, 1999;Suzuki and Sugiyama, 1999;Inui et al, 2000a;van Aubel et al, 2000;Gao and Meier, 2001) (Table 1). In recent years, a number of important transporters have been cloned, and considerable progress has been made in understanding the molecular characteristics of individual transporters.…”