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大鼠脑中多巴胺、3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)生成速率的动力学研究:对DOPAC来源的启示

A kinetic study of the rate of formation of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat: implications for the origin of DOPAC.

作者信息

Soares-da-Silva P, Garrett M C

机构信息

Laboratório de Farmacologia, Faculdade de Medicina, Porto, Portugal.

出版信息

Neuropharmacology. 1990 Oct;29(10):869-74. doi: 10.1016/0028-3908(90)90135-e.

DOI:10.1016/0028-3908(90)90135-e
PMID:1979427
Abstract

The rates of disappearance of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of rats treated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine were measured. Levels of dopamine. DOPAC and HVA in tissue were quantified in the striatum, nucleus accumbens and frontal cortex of the rat by means of high pressure liquid chromatography with electrochemical detection. Rats were sacrificed 1, 2 or 3 hr after the administration of alpha-methyl-p-tyrosine (200 mg/kg, i.p.). Levels of dopamine, DOPAC and HVA in tissue were logarithmically transformed, plotted against the duration of inhibition of tyrosine hydroxylase and the rate constant of the decline of dopamine and of its metabolites calculated. The rate constant of decline of DOPAC in each of brain studied was found to be greater than that for dopamine. The rate constant for the decline of dopamine was found to be greater in areas of the brain presenting the largest DOPAC/dopamine tissue ratios (frontal cortex greater than nucleus accumbens greater than striatum). The present results suggest that a substantial amount of DOPAC in brain derives from a newly formed pool of dopamine.

摘要

测定了用酪氨酸羟化酶抑制剂α-甲基-p-酪氨酸处理的大鼠脑中多巴胺、3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的消失速率。通过带有电化学检测的高压液相色谱法对大鼠纹状体、伏隔核和额叶皮质组织中的多巴胺、DOPAC和HVA水平进行定量。在给予α-甲基-p-酪氨酸(200mg/kg,腹腔注射)后1、2或3小时处死大鼠。将组织中多巴胺、DOPAC和HVA的水平进行对数转换,绘制其与酪氨酸羟化酶抑制持续时间的关系图,并计算多巴胺及其代谢产物下降的速率常数。发现在所研究的每个脑区中,DOPAC下降的速率常数大于多巴胺下降的速率常数。在脑内呈现最大DOPAC/多巴胺组织比值的区域(额叶皮质>伏隔核>纹状体),发现多巴胺下降的速率常数更大。目前的结果表明,脑内大量的DOPAC来源于新形成的多巴胺池。

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