The activity of MAO A and B in rat renal cells and tubules.
The present study reports on the presence of type A and B monoamine oxidase (MAO) activity and their sensitivity to selective MAO-A and MAO-B inhibition by Ro 41-1049 and lazabemide, respectively, in homogenates of isolated rat renal tubules. Non-linear analysis of the saturation curve of H-5-hydroxytryptamine (3H-5-HT ) deamination revealed a Km of 351+/-71 microM (n=4) and a Vmax of 25+/-2 nmol mg protein(-1) h(-1). Deamination of 14C-beta-phenylethylamine (14C-beta-PEA) was also a saturable process yielding Km values of 58+/-12 microM and Vmax values of 24+/-2 nmol mg protein(-1) h(-1). Ro 41-1049 produced a concentration-dependent inhibition of 3H-5-HT deamination with a Ki of 24 nM. Deamination of 14C-beta-PEA was found to be reduced by lazabemide in a concentration-dependent manner with a Ki value of 17 nM. The effect of these selective MAO inhibitors on dopamine fate and DOPAC formation in isolated tubular epithelial cells was also studied. In these studies a clear inhibition of DOPAC formation was observed with Ro 41-1049 (250 nM), while 250 nM lazabemide was found not to increase the accumulation of newly-formed DA in those tubular epithelial cells loaded with 50 microM L-DOPA. In conclusion, the results presented here confirm the presence of both MAO-A and MAO-B activity in renal tubular epithelial cells, that MAO-A is the predominant enzyme involved in the deamination of the natriuretic hormone dopamine and that the deamination of newly-formed dopamine is a time-dependent process which occurs early after the decarboxylation of L-DOPA.
Guimarães
J T
JT
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Soares-da-Silva
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D007684:Kidney Tubules / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; C063456:Ro 41-1049; C059303:lazabemide; D008995:Monoamine Oxidase; D004298:Dopamine