Role of the liver in metabolism of DL-norepinephrine-14C

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Abstract
Isolated perfused rat livers were able to inactivate rapidly large amounts of circulating DL-norepinephrine. This was done by 1) O-methylation to normetan-ephrine, which was then conjugated with gluconic acid and excreted in bileorblood, or 2) oxidativedeamlnation and conversion to 3-methoxy-4-hydroxyphenylglycol, which was conjugated with sulfate and excreted in a similar manner. Small amounts of these metabolites were found, both free and conjugated, in the liver after a 5-hr perfusion. The amount of metabolites of norepinephrine excreted in bile of rats with biliary fistula was determined by its availability to the liver. When norepinephrine was injected into the tail vein, only 10% was metabolized and excreted in the bile in 5 hr, in contrast to 20% after intraportal infusion. Of the total biliary metabolite excretion, 70% was absorbed from the duodenum and subsequently excreted in the urine. Extrahepatic tissues can also Inactivate norepinephrine by formation of normetane-phrine and 3-methoxy-4-hydroxyphenylglycol and their conjugates. However, in the rat, metabolism of norepinephrine proceeded more slowly after hepatectomy and larger proportions of unchanged norepinephrine were excreted in the urine.