ALTERED GUANOSINE AND GUANINE CONCENTRATIONS IN RABBIT STRIATUM FOLLOWING INCREASED DOPAMINE TURNOVER

The significance of guanine nucleotides and nucleosides in neurodegene rative disorders is suggested by recent reports that these molecules e nhance neurite branching and astrocyte proliferation. The objective of this study was to investigate the influence of increased dopamine met abolism, produced by 5-day treatment of rabbits with reserpine (2 mg/k g) or levodopa (LD) (50 mg/kg), on striatal concentrations of guanosin e, guanine, and their metabolites. Reserpine treatment decreased stria tal guanosine by 41% and increased guanine by 50%, while LD decreased guanosine by 48% (all p < 0.01 vs. vehicle-treated controls). LD also increased guanine by 22% (not statistically significant). Xanthine and uric acid concentrations were unchanged. Because of the neurotrophic properties of guanosine and guanine, changes in striatal concentration s of these purines secondary to increased dopamine (DA) turnover may h ave relevance for survival of remaining dopaminergic neurons in Parkin son's disease (PD). (C) 1998 Elsevier Science Inc.