Role of monoamine oxidase and cathecol-O-methyltransferase in the metabolism of renal dopamine
Incubation of slices of rat renal cortex with 50 μM L-DOPA during 15 min resulted in the formation of dopamine and of its deaminated (3,4-dihydroxyphenylacetic acid; DOPAC), methylated (3-methoxytyramine; 3-MT) and deaminated plus methylated (homovanillic acid; HVA) metabolites. The presence of pargyline (100 μM) resulted in a 90% reduction in the formation of DOPAC and HVA; levels of dopamine and 3-MT were found to be significantly increased. A concentration dependent decrease in the formation of methylated metabolites was obtained in the presence of (10, 50 and 100 μM) tropolone (10–50% reduction) and (0.1, 0.5, 1.0 and 5.0 μM) RO 40-7592 (50–95% reduction). Ro 40-7592 was also found to significantly increase DOPAC (20–40%) and dopamine (10–30%) levels, whereas tropolone slightly increased DOPAC (10%) levels. These results show that deamination represents the major pathway in the metabolism of newly formed dopamine under in vitro experimental conditions in the rat kidney. In addition, only when MAO is inhibited does methylation appear to represent an alternative metabolic pathway.
KeywordsMonoamine Oxidase Sodium Butyrate Homovanillic Acid COMT Inhibitor COMT Activity
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