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

• Published in: American journal of physiology. Renal physiology Vol. 284; no. 1; p. F167
• Main Authors: Pizzinat, Nathalie, Marchal-Victorion, Sophie, Maurel, Agnes, Ordener, Catherine, Bompart, Guy, Parini, Angelo
• Format: Journal Article
• Language: English
• Published: United States 01-01-2003
• Subjects: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases - metabolism; Animals; Bromocriptine - pharmacology; Cells, Cultured; Dopamine - pharmacology; Dopamine Agonists - pharmacology; Enzyme Activation - drug effects; Enzyme Activation - physiology; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - physiology; Glomerular Mesangium - cytology; Glomerular Mesangium - enzymology; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - enzymology; Monoamine Oxidase - genetics; Monoamine Oxidase - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2 - metabolism; RNA, Messenger - analysis; Substrate Specificity
• ISSN: 1931-857X
• DOI: 10.1152/ajprenal.00113.2002

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 approximately 80% after 48-h incubation with the D(2)-like receptor agonist bromocriptine and quinpirole but not with the D(1)-like receptor agonist SKF-38393. This effect was prevented by the D(2)-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 D(2)-like receptors, inhibition of the cAMP-PKA pathway, and an ex novo enzyme synthesis.