Thymidine Transport in the Central Nervous System

Abstract

The mechanisms by which thymidine enters and leaves brain, choroid plexus and CSF were investigated by injecting [3H]thymidine i.v. and intraventricularly. [3H]Thymidine, with and without unlabeled thymidine, was infused at a constant rate into conscious adult rabbits. At 150 min [3H]thymidine readily entered CSF, choroid plexus and brain. In brain about 45% of the nonvolatile radioactivity was [3H]thymidine phosphates. The addition of 0.21 mmol/kg unlabeled thymidine to the infusion syringe decreased the phosphorylation of [3H]thymidine in brain by about 85%; the addition of 2.1 mmol/kg of unlabeled thymidine to the infusion syringe decreased the relative entry of [3H]thymidine into CSF and brain by 40 and 78%, respectively. Two h after intraventricular injection of [3H]thymidine, [3H]thymidine was rapidly cleared from CSF. Some entered the brain where about 40% of the [3H]thymidine was converted to [3H]thymidine phosphates. The intraventricular injection of unlabeled thymidine (21 .mu.mol) with the [3H]thymidine abolished the phosphorylation of [3H]thymidine in brain and significantly decreased the clearance of [3H]thymidine from the CSF. Rabbit brain slices accumulated [3H]thymidine by an energy-dependent, saturable high-affinity system that partially depended on intracellular phosphorylation of the [3H]thymidine. The entry of thymidine from blood into CSF, the extracellular space of brain and then into brain cells apparently involves 1 or more saturable transport and/or metabolic steps.