Angiotensin II induction of AP-1 in neurons requires stimulation of PI3-K and JNK

Abstract

Angiotensin II (Ang II) acts via its type 1 (AT 1) receptor in neurons to regulate the activity of multiple intracellular signaling molecules, including intracellular Ca 2+, protein kinase C, phosphatidylinositol 3-kinase (PI3-K), and c-Jun NH 2-terminal kinase (JNK). The present studies investigated the upstream signaling molecules involved in the Ang II stimulation of activator protein-1 (AP-1) DNA binding in neurons. Treatment of neurons cultured from neonatal rat hypothalamus and brainstem with Ang II (100 nM) showed a time-dependent increase in AP-1 DNA binding and this effect was inhibited by the AT 1 receptor antagonist, losartan (1 μM), the PI3-K inhibitor, LY294002 (10 μM), and the JNK inhibitor, JNK inhibitor II (100 nM). Furthermore, Ang II (100 nM) causes a time-dependent increase in JNK activity which was attenuated by PI3-K inhibition. These data establish, for the first time, a signaling cascade involved in the Ang II activation of AP-1 DNA binding in neurons.