THE CHARACTERISTICS OF BASOLATERAL NUCLEOSIDE TRANSPORT IN THE PERFUSED SHEEP CHOROID-PLEXUS AND THE EFFECT OF NITRIC-OXIDE INHIBITION ON THESE PROCESSES

The single pass paired dilution technique was used to measure the upta ke of nucleosides across the basolateral face of the isolated in situ perfused sheep choroid plexus (CP). The uptake of labelled adenosine a nd guanosine into the CP was large (approximate to 35%) whereas that o f thymidine was less (approximate to 15%). The addition of 0.5 mM unla belled adenosine to the perfusate inhibited the uptake of labelled ade nosine by 66%, guanosine by 100% and that of thymidine by 50%, whereas the addition of 0.5 mM unlabelled thymidine caused complete self-inhi bition. The backflux of adenosine was very small which may indicate a high rate of cellular metabolism or a flux into cerebrospinal fluid (C SF). The addition of 0.5 mM unlabelled adenosine did not alter the bac kflux of adenosine, but increased that of guanosine and thymidine. The entry of radioactivity derived from adenosine across the apical side of the CP cells into the newly formed CSF was determined as a 'CSF upt ake index' relative to [C-14]butanol and found to be about 25%; howeve r, HPLC analysis revealed that the majority of this activity was hypox anthine, and not adenosine. The complete inhibition of nitric oxide sy nthase caused a significant reduction in adenosine uptake into the CP and an increase in backflux for this molecule. It would appear that th e uptake for adenosine by the CP is governed by the rate of cellular m etabolism and not by the rate of transport into the cells of the choro id plexus whereas for guanosine and thymidine, transport is of greater importance. (C) 1997 Elsevier Science B.V.