title: Saturation kinetics, specificity and NBMPR sensitivity of thymidine entry into the central nervous system.
abstract: 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.
authors.affiliation: Sherrington School of Physiology, UMDS St. Thomas' Hospital Campus, University of London, UK. sarah.thomas@umds.ac.uk
authors.forename: S A
authors.initials: SA
authors.lastname: Thomas
authors.forename: M B
authors.initials: MB
authors.lastname: Segal
mesh_terms: D000345:Affinity Labels / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007700:Kinetics; D012680:Sensitivity and Specificity; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013936:Thymidine / Q000493:pharmacokinetics*
chemical_list: D000345:Affinity Labels; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D013936:Thymidine