Influence of tetrahydrobiopterin on serotonin synthesis, metabolism and release in synaptosomes.
The effects of (6R)-5,6,7,8-tetrahydro-l-biopterin (BH(4)) 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 BH(4), the essential cofactor for tryptophan hydroxylase, was incubated with synaptosomes in concentrations varying from 10 to 200 ?M, there was no effect on 5-HT formation, metabolism or release. Concentrations of 1-2 mM BH(4) had strong inhibitory effects on 5-HT synthesis. The incubation of synaptosomes with tryptophan increased the synthesis of 5-HT, but BH(4) did not further increase this effect. BH(4) 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 BH(4) do not increase the synthesis and release of 5-HT. It is concluded from the present results that tryptophan hydroxylase is saturated with BH(4) in synaptosomes.
Wolf
W A
WA
Cellular and Clinical Neurobiology Program, Department of Psychiatry, Wayne State University School of Medicine and Lafayette Clinic, 951 E. Lafayette, Detroit, MI 48207, U.S.A.
Anastasiadis
P Z
PZ
Kuhn
D M
DM
Levine
R A
RA