Demethylation of 3-O-methyldopa in the kidney: a possible source for dopamine in urine.
The possibility that demethylation of 3-O-methyldopa (OM-dopa) in the kidney could provide a source for dopamine in the urine was explored in male Wistar rats aged 60-90 days, using in vivo and in vitro approaches. The results showed that endogenous OM-dopa is filtered, reabsorbed and extensively metabolized in the kidney. Infusion of OM-dopa into anesthetized rats increased significantly urinary excretion of Na+, dopa, dopamine, and 3,4 dihydroxyphenylacetic acid. Whole kidney homogenates, slices from renal cortex, and microdissected proximal tubules produced significant amounts of both dopa and dopamine when incubated with OM-dopa. Renal cortex slices produced dose-dependent amounts of dopa and dopa-mine when incubated with 1-100 microM OM-dopa. Incubation of microdissected proximal tubule segments with 1 microM OM-dopa produced a fourfold (P < 0.025) increment in dopa and a twofold (P < 0.05) increment in dopamine (an effect similar to that observed with 1 microM L-dopa). One micromolar OM-dopa or 1 microM L-dopa decreased (P < 0.05) Na(+)-K(+)-adenosinetriphosphatase activity measured at maximal velocity condition in proximal tubules. In conclusion, these experiments show that in vitro the kidney is able to produce dopamine by demethylation of OM-dopa, while the results of the OM-dopa infusion suggest that this conversion may also occur in vivo.
Ibarra
F R
FR
Instituto de Investigaciones Medicas A. Lanari, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires, Argentina.
Aguirre
J
J
Nowicki
S
S
Barontini
M
M
Arrizurieta
E E
EE
Armando
I
I
D000818:Animals; D002396:Catechols / Q000652:urine; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis / Q000652:urine*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008745:Methylation; D009318:Natriuresis; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D002396:Catechols; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D000254:Sodium-Potassium-Exchanging ATPase; C008404:3-methoxytyrosine; D004298:Dopamine