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Tryptophan Uptake and Hydroxylation in Rat Forebrain Synaptosomes
Author(s) -
Knowles Richard G.,
Pogson Christopher I.
Publication year - 1984
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.1471-4159.1984.tb02736.x
Subject(s) - tryptophan hydroxylase , tryptophan , tryptamine , chemistry , veratridine , serotonin , hydroxylation , decarboxylation , synaptosome , biochemistry , endocrinology , medicine , enzyme , biology , sodium , amino acid , sodium channel , serotonergic , in vitro , organic chemistry , receptor , catalysis
Tryptophan uptake, hydroxylation, and decarboxylation in isolated synaptosomes were studied to assess how their properties may determine the rate of serotonin synthesis in the presynaptic nerve terminals of the brain. Simultaneous measurements of the rates of uptake, hydroxylation, and decarboxylation in the presence and absence of various inhibitors showed that tryptophan hydroxylase is rate‐limiting for serotonin synthesis in this model system. There was significant direct decarboxylation of tryptophan to tryptamine. Measurement of tryptophan hydroxylase flux with varying internal concentrations of tryptophan allowed the determination of the K m of tryptophan hydroxylase in synaptosomes for tryptophan of 120 15 μ M . Depolarisation of synaptosomes with veratridine caused both a reduction in the internal tryptophan concentration and an apparent activation of tryptophan hydroxylase. This activation did not occur in the absence of Ca 2+ or in the presence of trifluoperazine. Synaptosomal serotonin synthesis and brain stem‐soluble tryptophan hydroxylase were inhibited by low concentrations of noradrenaline or dopamine. Dibutyryl cyclic AMP, glucagon, insulin, and vasopressin were observed to have no effect on tryptophan uptake or hydroxylation in synaptosomes.