Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin and infusion of L-tyrosine on the in vivo L-[beta-C-11]DOPA disposition in the monkey brain

The effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BR-BH4) and L-tyrosine infusion on [C-11]dopamine synthesis was analyzed in the striatum of Rhesus monkey using positron emission tomography (PET). The rate for decarboxylation from L-[beta-C-11]DOPA to [C-11]dopamine was calculated using a graphical method with cerebellum as a reference region. Although the peripheral administration of 6R-BH4 at low dose (2 mg/kg) did not provide a significant increase in the rate of dopamine biosynthesis, a high dose of 6R-BH4 (20 mg/kg) induced an elevation of the rate. This 6R-BH4-induced elevation of the dopamine synthesis rate was further dose-dependently enhanced by the continuous infusion of L-tyrosine (0.2 and 1.0 mu mol/min/kg). L-Tyrosine infusion with a rate of 1.0 mu mol/min/kg caused an enhancement of the rate even during low dose administration of 6R-BH4 (2 mg/kg). L-Tyrosine infusion alone did not induce any elevation of the dopamine biosynthesis rate. The analysis of plasma indicated that the metabolic ratios of L-[beta-C-11]DOPA to each metabolite were not affected by 6R-BH4 and/or L-tyrosine infusion. The results suggest that the low dose loading of tyrosine facilitates the activity of 6R-BH4 on the presynaptic dopamine biosynthesis, and also that the combined effects can be monitored by PET using L-[beta-C-11]DOPA as a biochemical probe.