Purine and Pyrimidine Nucleoside Content of the Neuronal Extracellular Space in Rat

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.