| Saturation kinetics, specificity and NBMPR sensitivity of thymidine entry into the central nervous system. | |
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MedLine Citation:
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PMID: 9237518 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S A Thomas; M B Segal |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brain research Volume: 760 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 1997 Jun |
Date Detail:
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Created Date: 1997-10-28 Completed Date: 1997-10-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 59-67 Citation Subset: IM |
Affiliation:
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Sherrington School of Physiology, UMDS St. Thomas' Hospital Campus, University of London, UK. sarah.thomas@umds.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Affinity Labels
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pharmacology* Animals Biological Transport / physiology Central Nervous System / drug effects, metabolism* Dose-Response Relationship, Drug Guinea Pigs Kinetics Sensitivity and Specificity* Thioinosine / analogs & derivatives*, pharmacology Thymidine / pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Affinity Labels; 38048-32-7/4-nitrobenzylthioinosine; 50-89-5/Thymidine; 574-25-4/Thioinosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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