Abstract
A partially oxidized serotonin (5-HT) was synthesized electrochemically from 5-HT in an acidic solution. This compound was characterized by its chromatographic and electrochemical properties and identified by mass spectroscopy and NMR as tryptamine-4,5-dione (4,5-DKT). In in vitro superfusion experiments, 10(-5)M 4,5-DKT significantly increased the basal 5-HT efflux from both rat hippocampal and striatal fragments. In contrast, 10(-5) M 4,5-DKT did not change the release of dopamine or its metabolite, 3,4-dihydroxyphenylacetic acid from striatal fragments. Continuous perfusion of 4,5-DKT did not modify the effect of KCl on either 5-HT or dopamine release from both brain areas. In in vitro incubation experiments, 10(-8) to 10(-5) M 4,5-DKT evoked 5-HT efflux from rat hippocampus in a dose-dependent fashion. When 10(-4) and 10(-5) M fluoxetine was incubated with 10(-6) M 4,5-DKT, it partially blocked 4,5-DKT-induced 5-HT release. Pargyline, at 10(-5) M inhibited significantly the 5-hydroxyin-doleacetic acid efflux, but did not modify the 4,5-DKT-stimulated 5-HT release. Incubation of 4,5-DKT with glutathione (GSH) and mercaptoethanol indicated that 4,5-DKT binds to sulfhydryl groups. An evidence of GSH-4,5-DKT conjugate was also observed after incubation of 4,5-DKT with a brain homogenate. The interaction of 4,5-DKT with GSH or mercaptoethanol was blocked effectively with N-ethylmaleimide. It is possible that sulfhydryl groups are involved in the mechanism of 4,5-DKT action on 5-HT release.
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