Angiotensin AT(2) receptor stimulates ERK1 and ERK2 in quiescent but inhibits ERK in NGF-stimulated PC12W cells

To investigate the influence of AT(2) receptor stimulation on the ERK pathw ay and elucidate potential mechanisms of angiotensin II (ANG II)-mediated n euronal differentiation, we analysed tyrosine phosphorylation and activity of ERK after ANG II treatment of both quiescent and NGF-treated PC12W cells . Tyrosine phosphorylation of ERK1 and ERK2 corresponded with the activity of ERK. While ANG II induced an initial activation of ERK in quiescent cell s, the NGF-mediated plateau of ERK-stimulation was lowered by costimulation with ANG II. All effects of ANG II were sensitive to AT(2) - but not AT(1) receptor blockade. Ang II-mediated neurite outgrowth in PC12W cells was in hibited by co-treatment with the MEK inhibitor PD 098059. These findings de monstrate that the AT(2) receptor modulates ERK activity depending on the o verall cellular input. The distinct regulation of ERK by ANG II and NGF fur ther indicates basic differences in AT(2) receptor- and NGF-induced neurona l differentiation. (C) 2000 Published by Elsevier Science B.V.