Metabolism of 3-H-L-dopa by the rat gut in vivo-evidence for glucuronide conjugation.
Metabolism of 3-H-L-dopa by the rat gut in vivo-evidence for glucuronide conjugation.
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大鼠肠道体内 3-H-L-多巴的代谢——葡萄糖醛酸结合的证据。
DOI：
10.1016/0006-2952(75)90057-x
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发表时间：
1975
影响因子：
5.8
通讯作者：
Patricio Silva
中科院分区：
文献类型：
--
作者：
L. Landsberg;Martha B. Berardino;Patricio Silva
本文研究了~3H-L-多巴在大鼠体内的代谢。在一次静脉注射后。给大鼠十二指肠注射一定剂量的l-多巴后，大鼠十二指肠累积~3H-非儿茶酚代谢产物的速度远高于胃、脾和心脏。~3H-非儿茶酚主要定位于十二指肠粘膜，而不是肌层。在粘膜中，~3H-非儿茶酚占总~3H的90%，经氧化铝和Dowex层析分离后，大部分在氨基酸非儿茶酚部分。非儿茶酚代谢物在十二指肠黏膜中的蓄积不依赖于给药剂量的多巴；示踪剂量3-L-多巴后，氨基酸部分中~3H-非儿茶酚的百分比实际上增加了。十二指肠粘膜中多巴代谢产物的模式与其他组织有很大不同，但与肝脏、空肠和结肠相似。在注射~3H-L-多巴之前，通过胆总管插管分流胆汁并不改变十二指肠内代谢物的蓄积或模式。用谷氨酸酶和β-葡萄糖醛酸苷酶孵育、薄层层析和荧光分析等方法对十二指肠粘膜非儿茶酚氨基酸组分进行了分析，结果表明十二指肠粘膜积累的化合物主要是儿茶酚的葡醛酸偶联物，尤其是多巴胺。结论：循环中的多巴被大鼠肠黏膜摄取、脱羧化、结合和储存，主要以葡萄糖醛酸偶联物的形式存在。因此，肠道对循环中多巴的整体新陈代谢做出了重大贡献。此外，储存在肠道中的多巴代谢产物是儿茶酚的潜在储存库，可供生物体重新利用，这可能对人类的临床多巴药理学有重要意义。
The metabolism of intravenous3H-l-dopa by the rat gutin vivohas been studied. After a single i.v. bolus of a pharmacologic dose ofl-dopa, the rat duodenum accumulated3H-noncatechol metabolites of dopa at a far greater rate than stomach, spleen or heart.3H-noncatechols were localized predominantly in the duodenal mucosa and not the muscularis. In the mucosa,3H-noncatechols accounted for 90 per cent of the total3H, most of which was in the amino acid noncatechol fraction after Chromatographic separation on Alumina and Dowex. Accumulation of noncatechol metabolites in duodenal mucosa was not dependent on the administration of a pharmacologic dose of dopa; after a tracer dose of3-l-dopa the per cent of3H-noncatechols in the amino acid fraction actually increased. The pattern of dopa metabolites in duodenal mucosa was substantially different from a variety of other tissues, but was similar to liver, jejunum and colon. Diversion of the bile by cannulation of the common bile duct prior to the administration of3H-l-dopa did not change the accumulation or pattern of metabolites in the duodenum. Analysis of the noncatechol amino acid fraction from duodenal mucosa by incubation with Glusulase and β-glucuronidase, thin-layer chromatography, and fluorescent assay revealed that the compounds accumulated by duodenal mucosa were largely glucuronide conjugates of catechols, particularly dopamine. It is concluded that circulating dopa is taken up by the rat intestinal mucosa, decarboxylated, conjugated and stored, largely in the form of glucuronide conjugates. The gut thus makes a major contribution to the over-all metabolism of circulating dopa. Dopa metabolites stored in the gut, moreover, are a potential reservoir of catechols for reutilization by the organism, and this may have important implications for the clinical pharmacology ofl-dopa in man.