MECHANISMS OF NUCLEOBASE TRANSPORT IN RABBIT CHOROID-PLEXUS - EVIDENCE FOR A NA-DEPENDENT NUCLEOBASE TRANSPORTER WITH BROAD SUBSTRATE SELECTIVITY()

The overall goal of this study was to determine the mechanisms by whic h nucleobases are transported in the choroid plexus. Choroid plexus ti ssue slices were obtained from the lateral ventricles of rabbit brains and depleted of ATP with 2,4-dinitrophenol. In the presence of an ini tial inwardly directed Na+ gradient, hypoxanthine accumulated in the t issue slices against a concentration gradient, Na+-stimulated hypoxant hine uptake was saturable with a K-m of 31.1 +/- 9.71 mu M and a V-max of 2.69 +/- 0.941 nmol/g/s (mean +/- S.E.). Na+-stimulated hypoxanthi ne uptake was inhibited by (100) mu M naturally occurring purine and p yrimidine nucleobases (adenine, cytosine, guanine, hypoxanthine, thymi ne, uracil, and xanthine) as well as by the nucleoside analog, dideoxy adenosine. The stoichiometric coupling ratio between Na+ and hypoxanth ine was 1.7:1. The data demonstrate the presence of a novel Na+-depend ent nucleobase transporter in the choroid plexus, which is distinct ho m the previously described Na+-nucleoside transporter in choroid plexu s and from Na+-dependent nucleobase transporters in other tissues in t erms of its kinetics, substrate selectivity, and Na+-nucleobase stoich iometry. This transporter may play a role in the targeting of both sal vageable nucleobases and therapeutic nucleoside analogs to the central nervous system.