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.