The cerebral metabolism of L-dihydroxyphenylalanine. An autoradiographic and biochemical study.
The cerebral metabolism of L-dihydroxyphenylalanine. An autoradiographic and biochemical study.
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L-二羟基苯丙氨酸的脑代谢。
DOI：
10.1159/000137938
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发表时间：
1984
期刊：
影响因子：
3.1
通讯作者：
Wooten,GF
中科院分区：
文献类型：
--
作者：
Horne,MK;Cheng,CH;Wooten,GF
用自显影法研究了经卡比多巴预处理的大鼠静脉注射l- 3,4-二羟基苯基-(3-14C)- α - 9 （14c - l-多巴）后碳-14活性的脑区分布。14c - l -多巴给药后5min，碳-14脑区分布随脑血流的变化而变化。然而，从14c - l- dopa给药后45 min到4 h，碳-14活性以区域选择性的方式积累，与各区域内源儿茶酚胺含量相关（p < 0.001） （n = 26）。在服用14c - l -多巴后45分钟至4小时内，单侧黑质致密部损伤可显著减少同侧纹状体中碳-14的积累，而非对侧纹状体。同样，利血平预处理选择性地减少了碳-14在静脉注射14c - l -多巴后发生显著积累的区域的积累。采用液相色谱电化学检测法测定静脉注射3h - l -多巴后1 min ~ 4 h纹状体和小脑中l -多巴及其代谢物氚的含量。3h -多巴胺，以及随后的3h -二羟基苯乙酸和3h -同香草酸只出现在纹状体中。小脑和纹状体中3h -3- o -甲基多巴水平同时升高。这些结果表明，如果l -多巴可以用具有足够比活性的正电子发射同位素标记，那么通过正电子发射断层扫描对人体内多巴胺神经元进行成像是可行的。此外，这些结果表明，定量解释的图像是可能的。
The regional cerebral distribution of carbon-14 activity was studied using auto-radiography following the intravenous administration ofL-3,4-dihydroxyphenyl-(3-14C)-ala-nine (14C-L-dopa) to rats pretreated with carbidopa. 5 min after14C-L-dopa administration, the regional cerebral distribution of carbon-14 varied with regional cerebral blood flow. From 45 min to 4 h after14C-L-dopa administration, however, carbon-14 activity accumulated in a regionally selective manner which correlated (p < 0.001) with the total endogenous catechol-amine content of each region (n = 26). A prior unilateral lesion of the substantia nigra pars compacta markedly reduced the accumulation of carbon-14 in the ipsilateral, but not the contralateral, striatum at all times from 45 min to 4 h after14C-L-dopa administration. Similarly, reserpine pretreatment selectively reduced the accumulation of carbon-14 in only those regions in which a marked accumulation occurred in controls after intravenous injections of14C-L-dopa. Liquid chromatography with electrochemical detection was utilized to determine the tritium content ofL-dopa and its metabolites in the striatum and cerebellum from 1 min to 4 h after the intravenous administration of3H-L-dopa.3H-dopamine, and subsequently3H-dihydroxyphenylacetic acid and3H-homovanillic acid, appeared only in the striatum.3H-3-O-methyldopa levels rose simultaneously in the cerebellum and striatum. These results demonstrate a feasible approach for imaging dopamine neurons in man in vivo by positron emission tomography provided that L-dopa can be labeled with a positron-emitting isotope with sufficient specific activity. Furthermore, these results suggest that quantitative interpretation of the images is possible.