Nucleoside transport in choroid plexus: Mechanism and specificity

Abstract

In vitro the transport into and release of [ 3H]thymidine, [ 3H]deoxyuridine, and [ 3H]nitrobenzylthioinosine (NBTI) from the isolated choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, were studied separately. Using the ability of NBTI to inhibit nucleoside efflux from the choroid plexus, the transport of [ 3H]thymidine and [ 3H]deoxyuridine into the choroid plexus at 37 °C was measured. Like thymidine, deoxyuridine was transported into the choroid plexus against a concentration gradient by a saturable process that depended on intracellular energy production but not intracellular binding or metabolism. The Michaelis-Menten constants ( K T ) for the active transport of thymidine and deoxyuridine into the choroid plexus were 13.6 and 7.2 μM, respectively. Deoxyuridine and adenosine were competitive inhibitors of thymidine transport into the choroid plexus with inhibitor constants ( K I ) of 6.8 and 14.5 μM, respectively. [ 3H]NBTI was also transported into the choroid plexus at 37 °C; unlike [ 3H]thymidine and [ 3H]deoxyuridine, the release of [ 3H]NBTI was not inhibited by NBTI itself. These studies provide evidence that the choroid plexus contains an active nucleoside transport system of low specificity for nucleosides, and a separate, saturable efflux system for nucleosides that is very sensitive to inhibition by NBTI. In vivo these systems transport nucleosides from blood into cerebrospinal fluid.