Anion exchanger mediates benzylpenicillin transport in rat choroid plexus

Transport characteristics of benzylpenicillin in the central nervous system was examined using ATP-depleted rat choroid plexus. In the presence of an outwardly directed Cl- gradient, accumulation of benzylpenicillin was stimulated markedly compared with the accumulation in the absence of Cl- gradient. Under Cl- gradient conditions, benzylpenicillin was accumulated transiently at a concentration approximately 1.7-fold higher than at equilibrium ("overshoot") implying the uphill transport. The Cl- gradient-stimulated accumulation of benzylpenicillin was not solely due to the changes in the membrane potential or in the intracellular pH. Accumulation of benzylpenicillin in choroid plexuses preloaded with HCO3-, SCN- or benzylpenicillin also was stimulated compared with the accumulation in unpreloaded choroid plexuses. The Cl- gradient-stimulated benzylpenicillin accumulation was saturable (Km = 13.6 microM and Vmax = 3.76 nmol/ml of tissue per min), and was reduced by sulfhydryl reagents (p-hydroxymercuribenzoic acid, p-chloromercuribenzoic acid, p-chloromercuribenzenesulfonic acid and N-ethylmaleimide). Probenecid and anionic exchange inhibitors (furosemide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) inhibited the Cl- gradient-stimulated benzylpenicillin accumulation in a dose-dependent fashion. An inwardly directed Na+ gradient did not stimulate the accumulation of benzylpenicillin. These findings suggest that the principal mechanism for the uphill transport of benzylpenicillin in the rat choroid plexus is via an anionic exchanger.