The concentrations of the 5-S-cysteinyl adducts of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) and the levels of noradrenaline (NA), DA, DOPAC and DOPA were determined in the putamen (PUT), caudate nucleus (CN) and substantia nigra (SN) of human post mortem brains with or without depigmentation and degeneration of the SN. The levels of DA, DOPAC and DOPA decreased with the degree of depigmentation and degeneration in the three brain regions while NA levels only decreased in SN and PUT. In general, the concentrations of the 5-S-cysteinyl adducts did not differ, but the ratios of 5-S-cysteinyl-DA/DA, 5-S-cysteinyl-DOPAC/DOPAC and 5-S-cysteinyl-DOPA/DOPA were higher in patients with a more depigmentated and degenerated SN, except for the 5-S-cysteinyl-DA/DA ratio in the PUT. Higher ratios were also found in the cell body areas compared to the neuron terminal areas. Thus depigmentation and degeneration of dopaminergic SN neurons, seem to be correlated to enhanced rates of autoxidation, possibly due to an impaired antioxidant capacity.

No 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Sprague-Dawley rats were anesthetized with chloral hydrate, and plastic cannulae were permanently implanted into the lateral ventricles. The animals then were allowed to recover for 1-2 days. L-Buthionine sulfoximine (L-BSO), a selective inhibitor of glutathione (GSH) synthesis, and 6-hydroxydopamine (6-OH-DA), a selective catecholaminergic neurotoxin, were administered intracerebroventricularly. The striatal concentrations of GSH and monoamines were determined by HPLC with electrochemical detection. Two injections of L-BSO (3.2 mg, at a 48-h interval) resulted in a 70% reduction of striatal GSH. 6-OH-DA (150 or 300 micrograms) reduced the concentrations of striatal dopamine and noradrenaline 7 days after the administration, but left the concentrations of 5-hydroxytryptamine unaltered. L-BSO treatment did not produce any changes in the levels of monoamines per se but it potentiated the catecholamine-depleting effect of 6-OH-DA in the striatum. Thus, GSH appears to suppress the toxicity of 6-OH-DA, probably by scavenging the toxic species formed during 6-OH-DA oxidation. In view of these results one may suggest an important role for GSH in catecholaminergic neurons: protecting against the oxidation of endogenous catechols.

Reserpine administration (5 mg/kg, i.p.) to guinea pigs resulted in marked and long lasting dopamine (DA) depletion and a rapid, short lasting, increase of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. A marked and sustained increase of the level of 5-S-cysteinyl-dopamine, which is an adduct presumably formed following autoxidation of DA, started 3-4 h following the DA and DOPAC changes. Only small changes in the levels of the 5-S-cysteinyl adducts of DOPAC and 3,4-dihydroxyphenylalanine (DOPA) were found.