Abstract (EN):
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-3-5-hydroxytryptamine (H-3-5-HT) deamination revealed a K-m of 351+/-71 mu M (n=4) and a V-max of 25+/-2 nmol mg protein(-1) h(-1). Deamination of C-14-beta-phenylethylamine (C-14-beta-PEA) was also a saturable process yielding K-m values of 58+/-12 mu M and V-max values of 24+/-2 nmol mg protein(-1) h(-1). Ro 41-1049 produced a concentration-dependent inhibition of H-3-5-HT deamination with a K-i of 24 nM. Deamination of C-14-beta-PEA was found to be reduced by lazabemide in a concentration-dependent manner with a K-i 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 mu M 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.
Language:
English
Type (Professor's evaluation):
Scientific
Contact:
Patricio.Soares@mail.telepac.pt
No. of pages:
11