108560-71-0Relevant articles and documents
Oxidation of serotonin by superoxide radical: Implications to neurodegenerative brain disorders
Wrona, Monika Z.,Dryhurst, Glenn
, p. 639 - 650 (1998)
Many new lines of evidence implicate both superoxide anion radical (O2.-) and biogenic amine neurotransmitters in the pathological mechanisms that underlie neuronal damage caused by methamphetamine (MA), glutamate- mediated oxidative toxicity, ischemia-reperfusion, and other neurodegenerative brain disorders. In this investigation the oxidation of 5- hydroxytryptamine (5-HT, serotonin) by an O2.- -generating system (xanthine/xanthine oxidase) in buffered aqueous solution at pH 7.4 has been studied. The major product of the O2.- -mediated oxidation of 5-HT is tryptamine-4,5-dione (T-4,5-D). However, O2.- and H2O2, cogenerated by the xanthine oxidase-mediated oxidation of xanthine to uric acid, together react with trace levels of iron that contaminate buffer constituents to give a chemically ill-defined oxo-iron species. This species mediates the oxidation of 5-HT to a C(4)-centered carbocation intermediate that reacts with 5-HT to give 5,5'-dihydroxy-4,4'-bitryptamine (4,4'-D) and with uric acid to give 9-[3-(2-aminoethyl)-5-hydroxy-1H-indol-4-yl]-2,6,8-triketo- 1H,3H,7H-purine (7) as the major products. These products differ from those formed in the HO.-mediated oxidation of 5-HT under similar conditions. When the reaction is carried out in the presence of the intraneuronal nucleophile glutathione (GSH), T-4,5-D is scavenged to give 7-(S-glutathionyl)tryptamine- 4,5-dione, whereas the putative carbocation intermediate is scavenged to give 4-(S-glutathionyl)-5-hydroxytryptamine. T-4,5-D also reacts with the sulfhydryl residues of a model protein, alcohol dehydrogenase, and inhibits its activity. Previous investigators have proposed that T-4,5-D is a serotonergic neurotoxin. This raises the possibility that T-4,5-D and perhaps other putative intraneuronal metabolites formed by the O2.-/H2O2/oxo- iron-mediated oxidations of 5-HT might be endotoxins that contribute to neurodegeneration in brain regions innervated by serotonergic neurons caused by MA, ischemia-reperfusion, and other neurodegenerative brain disorders.
Electrochemical oxidation of histamine and serotonin at highly boron- doped diamond electrodes
Sarada,Rao, Tata N.,Tryk,Fujishima
, p. 1632 - 1638 (2000)
The electrochemistry of histamine and serotonin in neutral aqueous media (pH 7.2) was investigated using polycrystalline, boron-doped diamond thin- film electrodes. Cyclic voltammetry, hydrodynamic voltammetry, and flow injection analysis (FIA) with amperometric detection were used to study the oxidation reactions. Comparison experiments were carried out using polished glassy carbon (GC) electrodes. At diamond electrodes, highly reproducible and well-defined cyclic voltammograms were obtained for histamine with a peek potential at 1.40 V vs SCE. The voltammetric signal-to-background ratios obtained at diamond were I order of magnitude higher than those obtained for GC electrodes at and above 100 μM analyte concentrations. A linear dynamic range of 3-4 orders of magnitude and a detection limit of 1 μM were observed in the voltammetric measurements. Well-defined sweep rate-dependent voltammograms were also obtained for 5-hydroxytryptamine (5-HT). The characteristics of the voltammogram indicated lack of adsorption of its oxidation products on the surface. No fouling or deactivation of the electrode was observed within the experimental time of several hours. A detection limit of 0.5 μM (signal-to-noise ratio 13.8) for histamine was obtained by use of the FIA technique with a diamond electrode. A remarkably low detection limit (10 nM) was obtained for 5-HT on diamond by the same method. Diamond electrodes exhibited a linear dynamic range from 10 nM to 100 μM for 5-HT determination and a range of 0.5-100 μM for histamine determination. The FIA response was very reproducible from film to film, and the response variability was below 7% at the actual detection limits.
Influence of L-Cysteine on the Oxidation Chemistry of Serotonin
Wrona, Monika Z.,Singh, Satendra,Dryhurst, Glenn
, p. 421 - 445 (1994)
L-Cysteine (CySH) intervenes in the normal electrochemically driven oxidation of 5-hydroxytryptamine (5-HT; serotonin) at physiological pH by scavenging the quinone imine proximate oxidation product of this indolic neurotransmitter to give 4-S-cysteinyl-5-hydroxytryptamine (4-S-CyS-5-HT). The latter cysteinyl conjugate is more easily electro-oxidized than 5-HT and, in the presence of free CySH, undergoes a complex series of reactions leading to 8-(2-aminoethyl)-1,2,3,5,6,9-hexahydro-5,9-dioxo-pyrrolobenzothiazine-2-carboxylic acid (20) and N--3-(2-aminoethyl)-1,4-dihydro-4-oxo-5H-indol-5-ylidene>-L-cysteine (4). CySH also reacts with another normal oxidation product of 5-HT, tryptamine-4,5-dione, to give 4 and 20. There is evidence that aberrant oxidative metabolism of 5-HT occurs in the brains of Alzheimer's Disease patients. In the event that such reactions occur in the cytoplasm of serotonergic nerve terminals or axons they would necessarily expose electrophilic intermediates and products to the intraneuronal nucleophiles CySH and GSH. The results of this study indicate that 4 and 20 might represent aberrant oxidative metabolites formed in such reactions. However, the ease of oxidation of 4-S-CyS-5-HT compared to 5-HT suggest that this conjugate is likely to be only a transient species in vivo under conditions where the neurotransmitter is oxidized.
