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Stimulation of the Serotonin Autoreceptor Prevents the Calcium‐Calmodulin‐Dependent Increase of Serotonin Biosynthesis in Rat Raphe Slices
Author(s) -
Sawada Makoto,
Nagatsu Toshiharu
Publication year - 1986
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.1471-4159.1986.tb13063.x
Subject(s) - serotonin , autoreceptor , tryptophan hydroxylase , medicine , endocrinology , raphe nuclei , serotonergic , chemistry , stimulation , tryptophan , biology , biochemistry , receptor , amino acid
The role of the serotonin (5‐hydroxytryptamine) autoreceptor in the regulation of the activity of tryptophan hydroxylase was investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measuring the accumulation of 5‐hydroxytryptophan in the presence of inhibition of aromatic L‐amino acid decarboxylase using 3‐hydroxy‐4‐bromobenzyloxy‐amine by HPLC with fluorescence detection. Serotonin and its agonists N, N‐dimethyl‐5‐methoxytryptamine and 1‐(m‐chlorophenyl)‐piperazine reduced the formation of 5‐hydroxytryptophan to 50–60% at 10 −5 M . The effect of serotonin was reversed by 10 −5 M methiothepin. an antagonist of the serotonin autoreceptor. The calmodulin antagonists N‐(6‐aminohexyl)‐5‐chloro‐1 ‐naphthalenesul‐fonamide (W‐7) and N‐(6‐ammohexyl)‐1‐naphthalenesulfonamide (W‐5), dose‐dependently reduced the basal formation of 5‐hydroxytryptophan to 40–50% at 10 −6 and 10 −4 M , respectively. W‐7 also reduced the activated formation by A‐23187 or dibutyryl cyclic AMP in a dose‐dependent manner. W‐7 had no effect on 5‐hydroxytryptophan formation reduced by serotonin at 10 −5 M . These results suggest that the role of the serotonin autoreceptor was related to the prevention of the calcium‐calmodulin‐dependent activation of tryptophan hydroxylase.