The effects of (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4) on the uptake of tryptophan, its conversion to serotonin (5-HT) and 5-hydroxyindoleacetic acid and on the basal release of 5-HT was studied in rat brain synaptosomes. When BH4, the essential cofactor for tryptophan hydroxylase, was incubated with synaptosomes in concentrations varying from 10 to 200 μM, there was no effect on 5-HT formation, metabolism or release. Concentrations of 1-2 mM BH4 had strong inhibitory effects on 5-HT synthesis. The incubation of synaptosomes with tryptophan increased the synthesis of 5-HT, but BH4 did not further increase this effect. BH4 was taken up into synaptosomes in a concentration-dependent manner under all incubation conditions and was stable in the chemically reduced (tetrahydro-) form. These results indicate that increases in the synaptosomal concentration of BH4 do not increase the synthesis and release of 5-HT. It is concluded from the present results that tryptophan hydroxylase is saturated with BH4 in synaptosomes.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology