DOPAMINE ACTIVATES ERK1/2 IN PROXIMAL TUBULE CELLS: ROLE OF PKC, PKA AND REACTIVE OXYGEN SPECIES

ACQUIER A; MORI SEQUEIROS GARCÍA MM; PAZ C; MENDEZ CF

San Miguel de Tucumán; Tucumán, Argentina

Congreso; XLV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

In the proximal tubule, dopamine (DA) regulation of Na+,K+-ATPase involves the activation of D1- and D2-like receptors, stimulation of PKC and PKA, PLA2-mediated arachidonic acid (AA) release and generation of hydroxylated metabolites of AA. Since the activity of cytosolic PLA2 is regulated by protein phosphorylation, we aimed to study the effect of DA on ERK1/2 activity and its possible role in PLA2 activation. Opossum kidney cells were stimulated with DA or selective D1 (SKF-38393) or D2 (PPHT) agonists. DA (1 ìM, 5 min) induced ERK1/2 activation through D1 and D2 receptors, an effect abolished by an antioxidant or by monoaminooxidase (MAO), PKC and PKA inhibition but not by PLA2 inhibition. Immunocytochemistry and Western blot analysis showed that MEK1/2 inhibition blunted the effect of DA on ERK1/2 and PLA2. DA-induced ERK1/2 activation promoted no cell proliferation, measured 24, 48 and 72 hours after incubation. We conclude from our results that DA, acting through D1 and D2 receptors, promotes ERK1/2 activation via a mechanism that involves PKC and PKA activities and the production of ROS by MAO-dependent DA metabolism. We also suggest that PLA2 is a downstream effector of ERK1/2.