Substrate-dependent regulation of MAO-A in rat mesangial cells: involvement of dopamine D2-like receptors.
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.
Pizzinat
Nathalie
N
Institut National de la Santé et de la Recherche Médicale U388, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse Cedex 04, France.
Marchal-Victorion
Sophie
S
Maurel
Agnes
A
Ordener
Catherine
C
Bompart
Guy
G
Parini
Angelo
A
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000201:enzymology; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013379:Substrate Specificity
D000067956:Adenylyl Cyclase Inhibitors; D018491:Dopamine Agonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D008995:Monoamine Oxidase; D000262:Adenylyl Cyclases; D004298:Dopamine