The activity of MAO A and B in rat renal cells and tubules

Abstract

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 3H-5-hydroxytryptamine ( 3H-5-HT) deamination revealed a K m, of 351 ± 71 μM (n = 4) and a V max of 25 ± 2 nmol mg protein −1 h −1. Deamination of 14C-β-phenylethylamine ( 14C-β-PEA) was also a saturable process yielding K m values of 58 ± 12 μM and V max 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 K i of 24 nM. Deamination of 14C-β-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 μM 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.