In Vivo Autoxidation of Dopamine in Guinea Pig Striatum Increases with Age

Authors


Address correspondence and reprint requests to Dr. B. Fornstedt at Department of Pharmacology, University of Göteborg, P.O. Box 33031, S-400 33 Göteborg, Sweden.

Abstract

Catechols are known to react readily with molecular oxygen to form the corresponding quinones together with reduced oxygen species. These products have been shown to be toxic in in vivo and in vitro systems. 5-S-Cysteinyl adducts of catechols are believed to be formed through the spontaneous reaction between quinones and thiol-containing compounds, like cysteine and glutathione (GSH). Thus, the brain levels of these adducts probably indicate the autoxidation rate of catechols in vivo. In the present study, the striatal concentrations of 5-S-cysteinyldopamine (5-S-cysteinyl-DA), 5-S-cysteinyl-3,4-dihydroxyphenylalanine (5-S-cysteinyl-DOPA), and 5-S-cysteinyl-3,4-dihydroxyphenylacetic acid (5-S-cysteinyl-DOPAC) were determined in 2-week-, 2-month-and 3-year-old guinea pigs. In addition, brain levels of DA, the DA metabolite DOPAC, and GSH were assessed. The concentration of 5-S-cysteinyl-DA increased markedly with age. The 3-year-old guinea pigs had the highest level, i.e., 248% of the concentration in the 2-week-old animals and 219% of the concentration in the 2-month-old animals. Furthermore, the striatal 5-S-cysteinyl-DOPA level in the 3-year-old group was 68% higher than in the 2-week-old group and 46% higher than in the 2-month-old group. No age difference in the striatal concentration of DA was found. In contrast, the concentration of DOPAC increased with age: The DOPAC level in the 3-year-old animals was 153% of the level in the 2-week-old animals and 116% of the level in the 2-month-old animals. A slight decrease in brain GSH content was observed between 2 weeks and 2 months, whereas the level in the 3-year-old animals was not significantly different from the concentration in the 2-month-old animals. Thus, the present study has shown an increase in 5-S-cysteinyl-DA and 5-S-cysteinyl-DOPA levels with age in guinea pig striatum. The rise in 5-S-cysteinyl-DA content was larger than the increase in content of the DA metabolite DOPAC, a finding indicating that DA to a greater extent undergoes autoxidation with increasing age. This may be part of the mechanism underlying the loss of dopaminergic neurons in senescence and in Parkinson's disease.

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