Edwards D J, Ravitch J, Knopf S, Sedlock M L
Biochem Pharmacol. 1985 Apr 15;34(8):1255-63. doi: 10.1016/0006-2952(85)90503-9.
The effects in rats of intraventricular injections of 6-hydroxydopamine (6-OHDA) on the urinary excretion 1-3 weeks later of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), p-hydroxyphenylglycol (pHPG), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were examined. The excretion of MHPG was decreased to 63 and 71% of control on days 7 and 14, respectively, but had returned to control levels by day 23, even though the brain levels were decreased by 87%. Free and total HVA excretion was reduced on both days 7 and 23, but free and total DOPAC was reduced only on day 7. Based on these data, it can be estimated that about 39% of the free and 46% of the total HVA in urine originates in the CNS. The excretion of conjugated HVA was decreased by 70-80%, but this decrease does not support the notion that the conjugated form of HVA is derived principally from the brain and thus serves as a better marker of brain dopamine metabolism, since the level of this metabolite in the brain was not correspondingly decreased but was instead increased. Urinary DOPAC levels were generally more variable and derived to a greater extent from the periphery; therefore, DOPAC appears to be less suitable than HVA as a marker of brain dopamine. The results also indicate that as much as 35% of the urinary MHPG may originate in the CNS, although compensatory changes in catecholamine metabolism in either the brain or in the periphery may have somewhat influenced this estimate. The results also suggest that at least as much pHPG as MHPG in urine derives from the CNS. The data are consistent with the idea that the neutral dopamine metabolites largely derive from the brain, but the relatively small depletion in their brain levels produced by 6-OHDA prevented the exact proportion being determined accurately.
研究了脑室内注射6-羟基多巴胺（6-OHDA）对大鼠1-3周后尿中3-甲氧基-4-羟基苯乙二醇（MHPG）、3,4-二羟基苯乙醇（DHPE）、3-甲氧基-4-羟基苯乙醇（MHPE）、对羟基苯乙二醇（pHPG）、高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC）排泄的影响。在第7天和第14天，MHPG的排泄量分别降至对照值的63%和71%，但到第23天时已恢复到对照水平，尽管脑内水平降低了87%。在第7天和第23天，游离和总HVA排泄均减少，但游离和总DOPAC仅在第7天减少。根据这些数据，可以估计尿中约39%的游离HVA和46%的总HVA来源于中枢神经系统。结合型HVA的排泄减少了70-80%，但这种减少并不支持以下观点，即结合型HVA主要来源于脑，因此可作为脑多巴胺代谢更好的标志物，因为该代谢产物在脑内的水平并未相应降低，反而升高。尿中DOPAC水平通常变化更大，且在更大程度上来源于外周；因此，DOPAC似乎不如HVA适合作为脑多巴胺的标志物。结果还表明，尿中高达35%的MHPG可能来源于中枢神经系统，尽管脑或外周儿茶酚胺代谢的代偿性变化可能对这一估计有一定影响。结果还提示，尿中pHPG至少与MHPG一样多来源于中枢神经系统。这些数据与中性多巴胺代谢产物主要来源于脑的观点一致，但6-OHDA导致其脑内水平相对较小的消耗，使得无法准确确定其确切比例。
