Substrate-dependent regulation of MAO-A in rat mesangial cells: involvement of dopamine D2-like receptors

Abstract

In the present study, we investigated the existence of a back-regulation of the catecholamine-degrading enzyme monoamine oxidase (MAO)-A by dopamine in rat renal cells. In proximal tubule cells, MAO-A expression was not modified after dopamine receptor stimulation. In contrast, in mesangial cells, enzyme assay and Western blots showed that MAO activity and protein increased by ∼80% after 48-h incubation with the D2-like receptor agonist bromocriptine and quinpirole but not with the D1-like receptor agonist SKF-38393. This effect was prevented by the D2-receptor antagonist sulpiride and domperidone. The increase in MAO-A protein was preceded by an augmentation of MAO-A mRNA that was prevented by the transcriptional inhibitor actinomycin D. Bromocriptine effect was mimicked by the PKA inhibitor H89 and inhibited by the PKA activator 8-bromo-cAMP. These results show for the first time the existence of a dopamine-dependent MAO-A regulation involving D2-like receptors, inhibition of the cAMP-PKA pathway, and an ex novo enzyme synthesis.