Increased serotonin efflux by a partially oxidized serotonin: tryptamine-4,5-dione.
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.
Chen
J C
JC
Department of Pharmacology and Experimental Therapeutics, Boston University Medical Center, Massachusetts.
Crino
P B
PB
Schnepper
P W
PW
To
A C
AC
Volicer
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007202:Indicators and Reagents; D045563:Indolequinones; D007700:Kinetics; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014363:Tryptamines / Q000138:chemical synthesis / Q000494:pharmacology*
D007202:Indicators and Reagents; D045563:Indolequinones; D014363:Tryptamines; D015102:3,4-Dihydroxyphenylacetic Acid; C060213:tryptamine-4,5-dione; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D011189:Potassium Chloride; D004298:Dopamine