Metabolism of ³H-l-dopa by the rat gut in vivo-evidence for glucuronide conjugation

The metabolism of intravenous ³H-l-dopa by the rat gut in vivo has been studied. After a single i.v. bolus of a pharmacologic dose of l-dopa, the rat duodenum accumulated ³H-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 total ³H, 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 of ³-l-dopa the per cent of ³H-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 of ³H-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 of l-dopa in man.