Purine and pyrimidine nucleoside content of the neuronal extracellular space in rat. An in vivo microdialysis study.

Abstract

Neurological side-effects of chemotherapeutic agents1 known to act on purine and pyrimidine metabolism enzymes raised a possible role for nucleosides and deoxynucleosides in brain cell survival as it is demonstrated in recent investigations.2–5 Some new data also demonstrated the involvement of nucleotides and nucleosides in various brain functions. Apart from the well-known transmitter function of ATP6 and neuromodulator role of adenosine7 other nucleotides and nucleosides have also been suggested to be neuroactive. Pyrimidine nucleotides have specific pyrimidinoceptors even in cells of brain origin.8 Nucleosides could have their own modulatory actions as indicated by sleep modifying effect of uridine.9 The in vivo measurement of nucleosides and related substances in behaving animals could be the following major contribution to understanding the mechanisms of neurological side-effects of chemotherapeutic agents and the functional roles of nucleosides in the brain. A recently developed method, the in vivo microdialysis technique was used in the present study. Dialysis measures the composition of local extracellular space under various experimental conditions in freely moving animals.10 The main applications of microdialysis technique is measuring synaptic neurotransmitter overflow,10 investigation of transport functions, and pharmacokinetics of various drugs,11 and also gaining information about intracellular metabolic processes.12 Microdialysis has already been applied in human patients13 with subarachnoidal haemorrhage, head trauma, Parkinson’s disease, brain tumors and epilepsy.