TY - JOUR
T1 - Further studies on catechol uptake and metabolism in rat small bowel in vivo
T2 - (1) A quantitatively significant process with distinctive structural specifications; and (2) the formation of a dopamine glucuronide reservoir after chronic l-dopa feeding
AU - Landsberg, Lewis
AU - Berardino, Martha B.
AU - Stoff, Jeffrey
AU - B. Young, James
N1 - Funding Information:
* Supported in part by the Milton Fund of Harvard University. a General Research Support Grant from the BethIsraelHospitalandNIHprants#HLI 1414andRR-76. A preliminary report was presented before the American Federation for Clinical Research in May. 1976 fClin. Res. XXIV. 36A. 1976).
PY - 1978/5/1
Y1 - 1978/5/1
N2 - Studies were performed to evaluate further the uptake and metabolism of l-dopa by the rat small bowel in vivo. After an intravenous (i.v.) infusion of [3H]-l-dopa, 9.5 per cent of the total dose infused was recovered from small bowel, an amount greater than that recovered in bile and liver combined. A homozygous Gunn rat resembled normal Sprague-Dawley rats in accumulation and metabolism of the [3H]-l-dopa. Labelled congeners of dopa were concentrated in duodenal mucosa so that the uptake of isoproterenol > epinephrine > norepinephrine = dopa > dopamine = octopamine > tyramine > phenylethylamine. Thus, functional groups on the phenyl ring, side chain, and amino group favored accumulation. The structural specificity was clearly distinct from uptake in the sympathetic nerve endings as reflected in a completely different uptake pattern in heart. Rats fed unlabelled l-dopa as part of a synthetic diet for eleven days accumulated large amounts of dopamine glucuronide in the small bowel (> 25 μg/g). The dopamine glucuronide in small bowel disappeared rapidly after withdrawal of dopa from the diet. These findings emphasize the important role of the gut in metabolizing endogenous and exogenous compounds related to the biologically important catecholamines.
AB - Studies were performed to evaluate further the uptake and metabolism of l-dopa by the rat small bowel in vivo. After an intravenous (i.v.) infusion of [3H]-l-dopa, 9.5 per cent of the total dose infused was recovered from small bowel, an amount greater than that recovered in bile and liver combined. A homozygous Gunn rat resembled normal Sprague-Dawley rats in accumulation and metabolism of the [3H]-l-dopa. Labelled congeners of dopa were concentrated in duodenal mucosa so that the uptake of isoproterenol > epinephrine > norepinephrine = dopa > dopamine = octopamine > tyramine > phenylethylamine. Thus, functional groups on the phenyl ring, side chain, and amino group favored accumulation. The structural specificity was clearly distinct from uptake in the sympathetic nerve endings as reflected in a completely different uptake pattern in heart. Rats fed unlabelled l-dopa as part of a synthetic diet for eleven days accumulated large amounts of dopamine glucuronide in the small bowel (> 25 μg/g). The dopamine glucuronide in small bowel disappeared rapidly after withdrawal of dopa from the diet. These findings emphasize the important role of the gut in metabolizing endogenous and exogenous compounds related to the biologically important catecholamines.
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U2 - 10.1016/0006-2952(78)90121-1
DO - 10.1016/0006-2952(78)90121-1
M3 - Article
C2 - 697938
AN - SCOPUS:0018179582
SN - 0006-2952
VL - 27
SP - 1365
EP - 1371
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 9
ER -