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Am J Physiol Renal Physiol (September 3, 2002). doi:10.1152/ajprenal.00113.2002
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Articles in PresS, published online ahead of print September 3, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00113.2002
Submitted on March 22, 2002
Accepted on August 28, 2002

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

Nathalie Pizzinat1, Sophie Marchal-Victorion1, Agnes Maurel1, Catherine Ordener1, Guy Bompart1, and Angelo Parini1*

1 Centre Hospitalier Universitaire Rangueil, Institut National de la Sante et de Recherche Medical U388, Institut Bugnard, Toulouse, France

* To whom correspondence should be addressed. E-mail: parini{at}toulouse.inserm.fr.

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 hours 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 8Br-cAMP. These results show for the first time the existence of a dopamine-dependent MAO A regulation involving D2-like receptors, inhibition of cAMP-PKA pathway and an ex novo enzyme synthesis.







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