SATURATION KINETICS, SPECIFICITY AND NBMPR SENSITIVITY OF THYMIDINE ENTRY INTO THE CENTRAL-NERVOUS-SYSTEM

It was not until the development of a technique that could measure the brain uptake of slowly moving substrates, that the saturable transpor t system at the blood-brain barrier (BBB) for the pyrimidine deoxyribo nucleoside, 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-nitrobenzy l)thio-9-beta-D-ribofuranosylpurine (NBMPR) sensitivity and saturation kinetics by means of the in situ brain perfusion technique in anaesth etized guinea pigs. The results indicated that the transport system id entified for [H-3]thymidine can also transport other pyrimidine deoxyr ibonucleosides (deoxycytidine) and pyrimidine ribonucleosides (uridine ) and is partially NBMPR-sensitive. In addition, guanosine, monocarbox ylic acids, hexoses or amino acids were not substrates for the transpo rt system. Further studies revealed that the transport system for [H-3 ]thymidine at the BBB has a low affinity (K-m 0.20 +/- 0.06 mM), but a relatively high capacity (V-max 1.06 +/- 0.08 nmol min(-1) g(-1)). Ov erall, this study is indicative of a NBMPR-sensitive (es) facilitative transport system for [H-3]thymidine and the likely presence of a NBMP R-insensitive and/or sodium-dependent transport system of the N2 (cit) type at the blood-brain and blood-CSF barriers of the guinea pig. (C) 1997 Elsevier Science B.V.