EXTRANEURONAL UPTAKE AND METABOLISM OF [H-3]L-NOREPINEPHRINE BY RAT DUODENAL MUCOSA

The effect of 6-hydroxydopamine on [3H]L-NE and [3H]L-dopa uptake in heart and duodenum was examined. In the heart 6-OHDA [6-hydroxydopamine] inhibited accumulation of 3H after [3H]L-NE but had no effect after [3H]L-dopa, demonstrating the efficacy of 6-OHDA pretreatment in destroying sympathetic nerve endings and indicating that dopa uptake in the heart is predominantly extraneuronal. In duodenal mucosa 6-OHDA pretreatment increased accumulation of [3H]L-dopa and [3H]L-NE, consistent with an extraneuronal site for the uptake process. In tests on the effect of 6-OHDA pretreatment on the metabolism of both [3H]L-NE and [3H]L-dopa in duodenal mucosa, 6-OHDA-pretreated rats produced the same pattern of metabolites as controls. [3H]L-NE metabolism resembled that of [3H]L-dopa; over 90% of the total 3H was in the form of noncatechols with a large portion in the amino acid fraction. The duodenal muscularis, contained 43% of the 3H in the catecholamine fraction. The endogenous NE content of the muscularis was 245.6 .+-. 26.2 compared with 45.6 .+-. 5.8 ng/g in the mucosa; most of the sympathetic nerve endings in duodenum are apparently in the muscularis. Conjugation of [3H]L-NE is probably a major pathway in duodenal mucosa as it is for [3H]L-dopa. Duodenal mucosa may possess an important inactivating mechanism for the catechol group. The gut is probably a potentially important site in the metabolic disposition of circulating catechols of endogenous origin.