Conversion of 3, 4-dihydroxyphenylalanine and deuterated 3, 4-dihydroxyphenylalanine to alcoholic metabolites of catecholamines in rat brain.
Conversion of 3, 4-dihydroxyphenylalanine and deuterated 3, 4-dihydroxyphenylalanine to alcoholic metabolites of catecholamines in rat brain.
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3, 4-二羟基苯丙氨酸和氘代 3, 4-二羟基苯丙氨酸在大鼠脑中转化为儿茶酚胺的酒精代谢物。
DOI：
10.1111/j.1471-4159.1981.tb00414.x
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发表时间：
1981
影响因子：
4.7
通讯作者：
Rizk,M
中科院分区：
文献类型：
--
作者：
Edwards,DJ;Rizk,M
本文用气相色谱-质谱联用选择离子监测的方法，研究了3，4-二羟基苯丙氨酸(3，4-二羟基苯丙氨酸-多巴)及其重氢类似物对大鼠脑内儿茶酚胺醇类代谢产物浓度的影响。单次腹腔注射l-DOPA可显著增加中性去甲肾上腺素代谢产物3-甲氧基-4-羟基苯乙二醇(MHPG)和3，4-二羟基苯乙二醇(DHPG)的浓度，并呈剂量依赖关系。MHPG和DHPG以及相应的多巴胺代谢产物在注射后1h达到最大值。注射150 mg/kgL-DOPA后1h，脑内MHPG和DHPG浓度分别升高78%和134%。对不同脑区的分析表明，除MHPG在小脑的增加幅度大于其他区域外，去甲肾上腺素代谢物的浓度在所有区域都是均匀升高的。后者的结果似乎是因为发现小脑中总MHPG的52%是非结合的(而在整个大脑中为15%)。l-DOPA导致小脑和脑干中游离MHPG的增加比例大于总MHPG的增加。通过用去氢的l-DOPA代替l-DOPA并同时测量去氢和非去氢去甲肾上腺素的代谢物，我们证明了几乎所有的MHPG和DHPG的增加都是由于外源性l-DOPA转化为去甲肾上腺素。因此，在试图了解l-DOPA的临床和行为效应时，需要考虑去甲肾上腺素代谢的影响。
We have investigated the effects of 3,4‐dihydroxyphenylalaninel‐DOPA) and its deuterated analogue on the concentrations of alcoholic metabolites of catecholamines in rat brain by means of gas chromatography/mass spectrometry with selected‐ion monitoring. Whole brain concentrations of the two neutral norepinephrine metabolites, 3‐methoxy‐4‐hydroxyphenylethylene‐glycol (MHPG) and 3,4‐dihydroxyphenylethyleneglycol (DHPG), were significantly increased in a dose‐dependent manner by a single intraperitoneal injection ofl‐DOPA. Both MHPG and DHPG, as well as the corresponding dopamine metabolites, reached a maximum 1 h after injection. Brain MHPG and DHPG concentrations were elevated by 78 and 134%, respectively, 1 h after injection of 150 mg/kgl‐DOPA. Analyses of discrete brain regions revealed that concentrations of the norepinephrine metabolites were elevated uniformly in all regions, except that MHPG showed a greater increase in the cerebellum than in other regions. The latter result appeared to be explained by the finding that 52% of the total MHPG in the cerebellum was unconjugated (compared to 15% in the whole brain).l‐DOPA caused a proportionately greater increase in free MHPG than in total MHPG in the cerebellum and brain stem. By using deuteratedl‐DOPA in place ofl‐DOPA and measuring both the deuterated and nondeuterated norepinephrine metabolites, we demonstrated that virtually all of the increases in MHPG and DHPG were due to the conversion of the exogenousl‐DOPA to norepinephrine. Thus, the effects of norepinephrine metabolism need to be considered in attempts to understand clinical and behavioral effects ofl‐DOPA.