REGIONAL AND SUBCELLULAR-DISTRIBUTION AND SOME FACTORS IN REGULATION OF REDUCED PTERINS IN RAT-BRAIN

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 4-20
Abstract
The regional and subcellular distribution, functional role and pharmacology of quinoid dihydropterin reductase (QDPR) and endogenous reduced pterins (PH4) subserving tyrosine hydroxylase (TOH) and tryptophan hydroxylase in the brain were studied. 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. A major portion of PH4 is probably associated with the biosynthetic activity of brain catecholaminergic systems. The regional and subcellular distribution of QDPR was incosistent 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. A major portion of total PH4 (as much as 90% in the striatum) is related to the function of catecholaminergic rather than serotonergic systems; PH4 level is a determinant of the velocity of DA synthesis, and PH4 levels are altered by some psychoactive drugs in association with changes in synaptosomal catecholamine biosynthetic rates.