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Effect of Tetrahydrobiopterin on Serotonin Synthesis, Release, and Metabolism in Superfused Hippocampal Slices
Author(s) -
Wolf William A.,
Ziaja Ellen,
Arthur Robert A.,
Anastasiadis Panagiotis Z.,
Levine Robert A.,
Kuhn Donald M.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08279.x
Subject(s) - serotonin , chemistry , endocrinology , tetrahydrobiopterin , medicine , tryptophan hydroxylase , extracellular , calcium , cofactor , serotonergic , biochemistry , biology , enzyme , receptor , organic chemistry
The effects of 6 R ‐5, 6, 7, 8‐tetrahydro‐L‐biopterin (6 R ‐BH 4 ), the in vivo cofactor for tryptophan hydroxylase, on the synthesis, release, and metabolism of serotonin were studied in superfused slices from rat hippocampus. 6 R ‐BH 4 did not alter the spontaneous release of [ 3 H]serotonin but it did significantly increase release when slices were depolarized with 30 m M KC1. Under the same incubation conditions, 6 R ‐BH 4 altered neither the synthesis (basal or tryptophan‐stimulated) nor the metabolism of serotonin in hippocampal slices. The synthetic pteridine 6‐methyl‐5, 6, 7, 8‐tetrahydropterin also augmented release under depolarizing conditions whereas biopterin, the oxidized form of 6 R ‐BH 4 , did not. The 6 S isotner of BH 4 , which is relatively inactive as a cofactor for tryptophan hydroxylase, was equipotent with 6 R ‐ BH 4 in stimulating serotonin release. 6 R ‐BH 4 did not inhibit serotonin uptake nor did it function as a serotonin autoreceptor antagonist to increase release. A direct serotonin releasing effect of 6 R ‐BH 4 , like that produced by p ‐chloroamphetamine, could also be ruled out. At suboptimal concentrations of extracellular calcium, the KC1‐induced release of 3 H was significantly reduced, yet the increase in release caused by BH 4 remained the same in magnitude. It is concluded that 6 R ‐BH 4 increases the depolarization‐induced release of serotonin through an interaction with the release mechanism itself, possibly by enhancing calcium influx or by increasing the sensitivity of the release mechanism to calcium. The effects of 6 R ‐BH 4 on serotonin release are independent from its function as the cofactor for tryptophan hydroxylase.