Dopamine activates ERK1/2 in proximal tubule cells: role of PKC, PKA and reactive oxygen species

ACQUIER, A.; MORI SEQUEIROS GARCIA, M.; PAZ, C.; MENDEZ, C.F.

San Miguel de Tucumán, Tucumán

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+-ATPaseinvolves the activation of D1- and D2-like receptors, stimulation ofPKC and PKA, PLA2-mediated arachidonic acid (AA) release andgeneration of hydroxylated metabolites of AA. Since the activity ofcytosolic PLA2 is regulated by protein phosphorylation, we aimedto study the effect of DA on ERK1/2 activity and its possible role inPLA2 activation. Opossum kidney cells were stimulated with DA orselective D1 (SKF-38393) or D2 (PPHT) agonists. DA (1 μM, 5min) induced ERK1/2 activation through D1 and D2 receptors, aneffect abolished by an antioxidant or by monoaminooxidase (MAO),PKC and PKA inhibition but not by PLA2 inhibition.Immunocytochemistry and Western blot analysis showed thatMEK1/2 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 fromour results that DA, acting through D1 and D2 receptors, promotesERK1/2 activation via a mechanism that involves PKC and PKAactivities and the production of ROS by MAO-dependent DAmetabolism. We also suggest that PLA2 is a downstream effector ofERK1/2.