TY - JOUR
T1 - Influence of tetrahydrobiopterin on serotonin synthesis, metabolism and release in synaptosomes
AU - Wolf, William A.
AU - Anastasiadis, Panagiotis Z.
AU - Kuhn, Donald M.
AU - Levine, Robert A.
N1 - Funding Information:
Acknowledgements--The research in this report was supported by the State of Michigan and, in part, by research grant 1RO3 MH44873 (DMK). W. A. Wolf was supported by a Postdoctoral Award from the Office of the Dean of the Medical School. P. Z. Anastasiadis is a Ph.D. student in the Cellular and Clinical Neurobiology Program and is supported by the Bodasaki Foundation (Athens, Greece). The authors are grateful to Sandra Demetriou for analyzing the samples for biopterin and BH4.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
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U2 - 10.1016/0197-0186(90)90111-6
DO - 10.1016/0197-0186(90)90111-6
M3 - Article
AN - SCOPUS:0025270443
SN - 0197-0186
VL - 16
SP - 335
EP - 340
JO - Neurochemistry International
JF - Neurochemistry International
IS - 3
ER -