EFFECT OF MONOAMINE OXIDASE INHIBITION ON BILIARY EXCRETION OF METABOLITES OF NOREPINEPHRINE BY ISOLATED RAT LIVER

¹ Sections of Biochemistry and Medicine, Mayo Clinic and Foundation, Rochester, Minnesota

An isolated liver perfusion system was used to study the effect of monoamine oxidase (MAO) inhibition on the biliary excretion of metabolites of DL- and L-norepinephrine(NE)-7-C¹⁴. From 0.2 to 15.0 µg of either DL- or L-NE were added to the perfusate; blood and bile flow remained normal in all experiments. Whole blood, plasma and bile were collected at intervals, and the distribution of C¹⁴ in free NE and its metabolites was studied. Free NE was isolated on an alumina column, and paper chromatographic methods were used to separate the metabolites. Addition of JB-516, a rapidly acting MAO inhibitor, produced an immediate effect consisting of decreased excretion of 3-methoxy-4-hydroxyphenylglycol sulfate (MHPG-S) in the bile and increased excretion of normetanephrine glucuronide (NMET-G) with parallel changes in levels of these metabolites in the perfusate, indicating that formation of NMET-G precedes formation of MHPG-S in the metabolism of circulating catecholamine by the isolated rat liver. Delayed MAO inhibition with the longer acting inhibitor, pargyline, led to decreased MHPG-S excretion without a compensatory increase in the O-methylated derivative, NMET-G, thus indicating MAO inhibition plus some decrease in O-methylation.