EFFECT OF 6R-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN ON IN-VIVO L-[BETA-C-11]DOPA TURNOVER IN THE RAT STRIATUM WITH INFUSION OF L-TYROSINE

L-[C-11]DOPA, combined with positron emission tomography (PET), has made possible the assessment of dopamine turnover in vivo. Before the evaluation of PET study with L-[C-11]DOPA in the primate, the effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (GR-BH4) and/or L-tyrosine infusion on L-[C-11]DOPA turnover was analyzed in the rat striatal tissue and in the striatal extracellular fluid using microdialysis. L-[C-11]DOPA was rapidly taken up into the brain after intravenous injection and converted to [C-11]dopamine, [C-11]DOPAC and [C-11]HVA in the striatal tissue. Small amount of 3-O-methyl-[C-11]DOPA, a product of DOPA by 3-O-methylation in peripheral tissues, was also detected in the striatal tissue. The striatum/cerebellum ratio of total radioactivity uptake was linear against time up to 40 min after L-[C-11]DOPA injection. The uptake ratio, increased by 6R-BH4 administration, was further increased by L-tyrosine infusion. The in vivo microdialysis technique was further applied to determine L-[C-11]DOPA and its metabolites in striatal extracellular fluid (ECF). The peripheral administration of 6R-BH4 (50mg/kg) induced elevation of [C-11]DOPA concentration in ECF in the early phase after injection, following higher radioactivity in [C-11]dopamine and [C-11]HVA fractions than those in control animals at late phase. The 6R-BH4-induced elevation of [C-11]DOPA uptake and the radioactivity of its metabolites was further enhanced by the continuous infusion of L-tyrosine at a dose of 1.0 mu mol/min/kg. L-Tyrosine infusion alone did not induce the elevation of radioactivity. The results suggest that [C-11]DOPA might be a useful probe to evaluate the effect of 6R-BH4, and/or L-tyrosine loading in the primate.