In vivo autoxidation of dopamine in guinea pig striatum increases with age.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Fornstedt
B
B
Department of Pharmacology, University of Göteborg, Sweden.
Pileblad
E
E
Carlsson
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism*; D003548:Cysteinyldopa / Q000031:analogs & derivatives / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D010084:Oxidation-Reduction
D015102:3,4-Dihydroxyphenylacetic Acid; C049277:5-S-cysteinyl-3,4-dihydroxyphenylacetic acid; D003548:Cysteinyldopa; C047408:5-S-cysteinyldopamine; D005978:Glutathione; D004298:Dopamine