AT2 receptor stimulation induces generation of ceramides in PC12W cells.

The angiotensin AT2 receptor has been implicated in both regeneration and apoptosis. To further investigate the molecular mechanisms leading to AT2 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 X 10(-6) M) increased ceramide levels by maximally 175% but did not affect sphingomyelin degradation. The ANG 11 effects were mediated by AT2 receptors since they were completely abolished by co-incubation with the AT2 receptor antagonist, PD123177 (10(-5) M), but not by the AT1 receptor antagonist, losartan (10(-5) M). These data suggest a novel signal transduction pathway to the AT2 receptor leading to apoptosis in neuronal cells.