Quantification of efflux into the blood and brain of intraventricularly perfused [3H]thymidine in the anaesthetized rabbit.
Studies using choroid plexuses incubated in vitro have led to the conclusion that pyrimidine deoxyribonucleosides, such as thymidine, enter the brain predominantly through the blood-cerebrospinal fluid (CSF) barrier across the choroid plexuses. In order to examine this hypothesis, ventriculocisternal perfusions were carried out to determine the magnitude of the passage of [3H]thymidine from the CSF into the brain and blood. These experiments demonstrated that approximately 50% of the [3H]thymidine was eliminated from the CSF perfusate, some 41.6 +/- 5.6% passing into the blood and only 7.6 +/- 0.6% to the brain. Efflux into both the blood and brain was saturable, with a Km of 17.8 microM and a Vmax of 0.46 nM min-1, and partially nitrobenzylthioinosine (NBMPR) sensitive. However, a non-saturable component did exist (Kd, 13.8 microliters min-1). Overall, the rapid removal of [3H]thymidine from the CSF and its low uptake from the CSF into the brain suggests that the choroid plexuses would be an inefficient pathway for the entry of this pyrimidine deoxyribonucleoside into the brain.
Thomas
S A
SA
Sherrington School of Physiology, UMDS, St Thomas' Hospital Campus, University of London, UK.
Davson
H
H
Segal
M B
MB
D000345:Affinity Labels; D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism; D005260:Female; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D011092:Polyethylene Glycols / Q000378:metabolism; D011817:Rabbits; D013868:Thioinosine / Q000031:analogs & derivatives; D013936:Thymidine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D000345:Affinity Labels; D011092:Polyethylene Glycols; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D013936:Thymidine