Fornstedt B, Carlsson A
Department of Pharmacology, University of Göteborg, Sweden.
Neuropharmacology. 1991 May;30(5):463-8. doi: 10.1016/0028-3908(91)90007-x.
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.
多巴胺(DA)、3,4-二羟基苯乙酸(DOPAC)和3,4-二羟基苯丙氨酸(DOPA)的5-S-半胱氨酰加合物在脑组织中的出现,似乎分别反映了DA、DOPA和DOPAC在体内的自氧化过程。与对照组相比,在用帕吉林(75mg/kg,腹腔注射,17小时)以及帕吉林加利血平(75mg/kg,腹腔注射,17小时加5mg/kg,腹腔注射,18小时)处理后,豚鼠纹状体和边缘系统中DOPAC和5-S-半胱氨酰-DOPAC的水平显著降低。然而,5-S-半胱氨酰加合物的消耗不如DOPAC严重,这表明加合物的周转较慢。单独使用帕吉林后,纹状体中多巴胺和5-S-半胱氨酰-DA均显著增加且增加程度相同。在边缘系统中,多巴胺显著增加,而5-S-半胱氨酰-DA的水平未发现变化。在用帕吉林加利血平处理后,纹状体中5-S-半胱氨酰-DOPA显著降低,单独使用帕吉林后则无显著变化。这些数据与单胺氧化酶抑制对儿茶酚自氧化有轻微抑制作用相符。然而,这种作用被多巴胺水平的升高所掩盖。