Effects of MAO-A and MAO-B selective inhibitors Ro 41-1049 and Ro 19-6327 on the deamination of newly formed dopamine in the rat kidney.
The present study has examined the effects of two selective inhibitors of monoamine oxidase (MAO) type A and B, respectively Ro 41-1049 and Ro 19-6327, on the deamination of newly synthesized dopamine (DA) in kidney slices incubated with exogenous L-3,4-dihydroxyphenylalanine (L-dopa; 1-100 microM). Ro 41-1049 (50, 100 and 250 nM) was found to produce a concentration-dependent increase of newly formed DA (36-56% increase) and reduced 3,4-dihydroxyphenylacetic (DOPAC) formation (45-86% reduction). Ro 19-6327 (50, 100 and 250 nM) was found not to affect the accumulation of newly formed DA up to 50 microM L-dopa in the medium, but significantly reduced the formation of DOPAC. At the concentration of 100 microM L-dopa, Ro 19-6327 (100 and 250 nM) significantly increased (by 32 and 132%, respectively), the DA tissue levels in kidney slices. Ro 19-6327 (100 and 250 nM) was found to decrease (30-70% reduction) DOPAC formation; this effect was also observed when tissues were incubated with L-dopa at concentrations lower than 50 microM. It is concluded that both MAO-A and MAO-B are important in the metabolism of newly formed DA in kidney slices incubated with exogenous L-dopa. The results also suggest that there at least two compartments in which newly formed DA can be deaminated.
Fernandes
M H
MH
Laboratório de Farmacologia, Faculdade de Medicina, Porto, Portugal.
Soares-da-Silva
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007668:Kidney / Q000033:anatomy & histology / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010848:Picolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; C063456:Ro 41-1049; C059303:lazabemide; D004295:Dihydroxyphenylalanine; D004298:Dopamine; D009638:Norepinephrine