AT(2) receptor stimulation induces generation of ceramides in PC12W cells

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 effe cts of angiotensin II (ANG II) on ceramide levels by HPTLC analysis. We cou ld demonstrate that ANG II time- (1-10 h) and dose-dependently (10(-8)-5x10 (-6) M) increased ceramide levels by maximally 175% but did not affect sphi ngomyelin degradation, The ANG II effects,were mediated by AT(2) receptors since they were completely abolished by co-incubation with the AT(2) recept or antagonist, PD123177 (10(-5) M), but not by the AT(1) receptor antagonis t, losartan (10(-5) M). These data suggest a novel signal transduction path way to the AT(2) receptor leading to apoptosis in neuronal cells. (C) 1999 Federation of European Biochemical Societies.