AT 2 receptor stimulation induces generation of ceramides in PC12W cells

Abstract

The angiotensin AT 2 receptor has been implicated in both regeneration and apoptosis. To further investigate the molecular mechanisms leading to AT 2 receptor-induced programmed cell death in PC12W cells we studied the effects of angiotensin II (ANG II) on ceramide levels by HPTLC analysis. We could demonstrate that ANG II time- (1–10 h) and dose-dependently (10 −8–5×10 −6 M) increased ceramide levels by maximally 175% but did not affect sphingomyelin degradation. The ANG II effects were mediated by AT 2 receptors since they were completely abolished by co-incubation with the AT 2 receptor antagonist, PD123177 (10 −5 M), but not by the AT 1 receptor antagonist, losartan (10 −5 M). These data suggest a novel signal transduction pathway to the AT 2 receptor leading to apoptosis in neuronal cells.