Effects of inhibition of monoamine oxidase on the levels of 5-S-cysteinyl adducts of catechols in dopaminergic regions of the brain of the guinea pig.
The occurrence of 5-S-cysteinyl adducts of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) in brain tissue, appears to reflect in vivo autoxidation of DA, DOPA and DOPAC, respectively. In the striatum and in the limbic system of guinea pig, the levels of DOPAC and 5-S-cysteinyl-DOPAC were markedly reduced after treatment with pargyline (75 mg/kg, i.p., 17 hr) and pargyline plus reserpine (75 mg/kg, i.p., 17 hr plus 5 mg/kg, i.p., 18 hr) compared to controls. However, the depletion of 5-S-cysteinyl adduct was less severe than that of DOPAC, suggesting a slower turnover of the adduct. Dopamine and 5-S-cysteinyl-DA increased significantly and to the same extent in the striatum, after pargyline alone. In the limbic system DA was significantly increased, whereas no change was found for levels of 5-S-cysteinyl-DA. 5-S-Cysteinyl-DOPA decreased significantly in the striatum after treatment with pargyline plus reserpine and non-significantly after pargyline alone. The data are compatible with a slight inhibitory effect of MAO inhibition on catechol autoxidation. This effect was, however, overridden by the increased level of DA.
Fornstedt
B
B
Department of Pharmacology, University of Göteborg, Sweden.
Carlsson
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002396:Catechols / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010293:Pargyline / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
D002396:Catechols; D015102:3,4-Dihydroxyphenylacetic Acid; D004295:Dihydroxyphenylalanine; D012110:Reserpine; C047408:5-S-cysteinyldopamine; D010293:Pargyline; D004298:Dopamine