Saturation kinetics, specificity and NBMPR sensitivity of thymidine entry into the central nervous system

Brain Res. 1997 Jun 20;760(1-2):59-67. doi: 10.1016/s0006-8993(97)00276-x.


It was not until the development of a technique that could measure the brain uptake of slowly moving substrates, that the saturable transport system at the blood-brain barrier (BBB) for the pyrimidine deoxyribonucleoside, thymidine, was demonstrated. The aim of this present study was to further characterize this saturable uptake system at the blood-brain and blood-CSF barriers in terms of specificity, 6-(4-nitrobenzyl)thio-9-beta-D-ribofuranosylpurine (NBMPR) sensitivity and saturation kinetics by means of the in situ brain perfusion technique in anaesthetized guinea pigs. The results indicated that the transport system identified for [3H]thymidine can also transport other pyrimidine deoxyribonucleosides (deoxycytidine) and pyrimidine ribonucleosides (uridine) and is partially NBMPR-sensitive. In addition, guanosine, monocarboxylic acids, hexoses or amino acids were not substrates for the transport system. Further studies revealed that the transport system for [3H]thymidine at the BBB has a low affinity (Km 0.20 +/- 0.06 mM), but a relatively high capacity (Vmax 1.06 +/- 0.08 nmol min(-1) g(-1)). Overall, this study is indicative of a NBMPR-sensitive (es) facilitative transport system for [3H]thymidine and the likely presence of a NBMPR-insensitive and/or sodium-dependent transport system of the N2 (cit) type at the blood-brain and blood-CSF barriers of the guinea pig.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affinity Labels / pharmacology*
  • Animals
  • Biological Transport / physiology
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism*
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Kinetics
  • Sensitivity and Specificity*
  • Thioinosine / analogs & derivatives*
  • Thioinosine / pharmacology
  • Thymidine / pharmacokinetics*


  • Affinity Labels
  • Thioinosine
  • 4-nitrobenzylthioinosine
  • Thymidine