The uptake of nucleobases was investigated across the basolateral membrane
of the sheep choroid plexus perfused in situ. The maximal uptake (U-max) fo
r hypoxanthine and adenine, was 35.51+/-1.50% and 30.71+/-0.49% and for gua
nine, thymine and uracil was 12.00+/-0.53%, 13.07+/-0.48% and 12.30+/-0.55%
, respectively with a negligible backflux, except for that of thymine (35.1
1+/-5.37% of the U-max). HPLC analysis revealed that the purine nucleobase
hypoxanthine and the pyrimidine nucleobase thymine can pass intact through
the choroid plexus and enter the cerebrospinal fluid CSF so the lack of bac
kflux for hypoxanthine was not a result of metabolic trapping in the cell.
Competition studies revealed that hypoxanthine. adenine and thymine shared
the same transport system, while guanine and uracil were transported by a s
eparate mechanism and that nucleosides can partially share the same transpo
rter. HPLC analysis of sheep CSF collected in vivo revealed only two nucleo
bases were present adenine and hypoxanthine; with an R-CSP/Plasma 0.19+/-0.
02 and 3.43+/-0.20, respectively. Xanthine and urate, the final products of
purine catabolism. could not be detected in the CSF even in truce amounts.
These results suggest that the activity of xanthine oxidase in the brain o
f the sheep is very low so the metabolic degradation of purines is carried
out only as far as hypoxanthine which then accumulates in the CSF. In concl
usion, the presence of saturable transport systems for nucleobases at the b
asolateral membrane of the choroidal epithelium was demonstrated. which cou
ld be important for the distribution of the salvageable nucleobases, adenin
e: and hypoxanthine in the central nervous system. (C) 2001 Elsevier Scienc
e B.V. All rights reserved.