Role of monoamine oxidase and catechol-O-methyltransferase in the metabolism of renal dopamine.
Incubation of slices of rat renal cortex with 50 microM 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 microM) 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 microM) tropolone (10-50% reduction) and (0.1, 0.5, 1.0 and 5.0 microM) 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.
Fernandes
M H
MH
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Soares-da-Silva
P
P
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000502:physiology*; D065098:Catechol O-Methyltransferase Inhibitors; D003470:Culture Media; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008995:Monoamine Oxidase / Q000502:physiology*; D009596:Nitrophenols; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D000077867:Tolcapone; D014334:Tropolone / Q000494:pharmacology
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D003470:Culture Media; D009596:Nitrophenols; D007980:Levodopa; D014334:Tropolone; D000077867:Tolcapone; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D004298:Dopamine