Saturable transport of valproic acid in rat choroid plexus in vitro.

In order to obtain in vitro evidence for a specific transport system of valproic acid (VPA) at the blood-cerebrospinal fluid (CSF) interface, the uptake of VPA by isolated rat choroid plexus was investigated. The uptake clearance of [3H]VPA decreased with the increase of the unlabeled VPA concentration in the incubation medium. Kinetic analysis yielded an apparent Km of 10.0 mM, Vmax of 0.0871 mumol s-1 g-1 and Kns, a permeability coefficient of the nonsaturable component, of 6.85 microL s-1 g-1, indicating that both saturable and nonsaturable systems may contribute to VPA uptake by choroid plexus. Organic anions, penicillin G, p-aminohippurate, salicylate, and probenecid significantly inhibited VPA uptake by choroid plexus. We suggest that VPA translocation through choroidal membrane is partly operated by the organic anion transport system. A significant decrease of VPA uptake induced by 2,4-dinitrophenol, stilbenedisulfonate, and hypothermia (10 degrees C) indicates the involvement of an energy-dependent, carrier-mediated transport system. These results demonstrate that VPA is actively transported through the rat choroidal epithelium via a saturable system probably shared by organic anions.