Regional and subcellular distribution and some factors in the regulation of reduced pterins in rat brain

Abstract

We have studied the regional and subcellular distribution, functional role, and pharmacology of quinoid dihydropterin reductase (QDPR) and endogenous reduced pterins (PH4) subserving tyrosin hydroxylase (TOH) and tryptophan hydroxylase in the rat brain. There is a significant correlation between the regional distribution of PH4 and TOH but not between PH4 and tryptophan hydroxylase or between either TOH or tryptophan hydroxylase and QDPR. This suggests that a major portion of PH4 is associated with the biosynthetic activity of brain catecholaminergic systems. The regional and subcellular distribution of QDPR was inconsistent with a regulatory function for QDPR in monoamine synthesis. In vitro measures of PH4, TOH, and synaptosomal dopamine (DA) and serotonin synthesis in the striate cortex of untreated animals and animals subjected to neurotoxin or electrolytic lesions of the dorsal raphe or substantia nigra exhibit significant covariation of PH4 with synaptosomal DA but not serotonin synthesis and a significant partial correlation of PH4 with DA synthesis. The subcellular distribution of PH4 in the striatum demonstrates an association of PH4 with the biosynthetic function of dopaminergic nerve terminals. Reserpine and d-amphetamine in vivo elicited an increase and decrease, respectively, in striatal PH4 paralleling induced changes in synaptosomal DA synthesis. Other drugs altering central catecholaminergic function did not alter striatal PH4 levels significantly. The data suggest that 1) a major portion of total PH4 (as much as 90% in the striatum) is related to the function of catecholaminergic rather than serotonergic systems, 2) PH4 levels is a determinant of the velocity of DA synthesis and 3) PH4 levels are altered by some psychoactive drugs in association with changes in synaptosomal catecholamine biosynthetic rates.