Serotonin acts as a radical scavenger and is oxidized to a dimer during the respiratory burst of activated microglia.
Serotonin (5-HT) is known to be readily oxidized and to act as a scavenger of reactive oxygen species produced, e.g., in the presence of peroxidase and H2O2 or during the respiratory burst of phagocytes. One major oxidation product formed under these conditions, the 5-HT dimer 5,5'-dihydroxy-4,4'-bitryptamine (DHBT), was suggested to have neurotoxic properties and to contribute to neuronal damage in neurodegenerative disorders. It is shown in the present study that the luminol-enhanced chemiluminescence signal measured after stimulation of the respiratory burst activity of cultivated rat microglial cells by the addition of phorbol 12-myristate 13-acetate is suppressed by 5-HT in a dose-dependent manner. During this process, 5-HT is oxidized to DHBT. Neither the intraventricular injection of DHBT nor the addition of DHBT to cultured astrocytes, neurons, or PC-12 cells was found to cause measurable cytotoxic effects. It is concluded that extracellular 5-HT locally released from platelets and 5-HT nerve endings at sites of brain damage or inflammation, through its suppressant effect on the release of reactive oxygen species during the respiratory burst of activated microglia, may contribute to attenuate secondary tissue damage in the CNS.
Huether
G
G
Department of Psychiatry, University of Göttingen, Germany.
Fettkötter
I
I
Keilhoff
G
G
Wolf
G
G
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D019281:Dimerization; D016166:Free Radical Scavengers; D007276:Injections, Intraventricular; D008163:Luminescent Measurements; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014363:Tryptamines / Q000008:administration & dosage / Q000494:pharmacology*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014363:Tryptamines; C076856:5,5'-dihydroxy-4,4'-bitryptamine; D012701:Serotonin; D013755:Tetradecanoylphorbol Acetate