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Am J Physiol Renal Physiol 284: F167-F174, 2003. First published September 3, 2002; doi:10.1152/ajprenal.00113.2002
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Vol. 284, Issue 1, F167-F174, January 2003

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

Nathalie Pizzinat*, Sophie Marchal-Victorion*, Agnes Maurel, Catherine Ordener, Guy Bompart, and Angelo Parini

Institut National de la Santé et de la Recherche Médicale U388, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse Cedex 04, France

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.

dopamine receptors; proximal tubule cells; monoamine oxidase A; 5-hydroxytryptamine


* N. Pizzinat and S. Marchal-Victorion contributed equally to this work.







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