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AT 2 receptor stimulation induces generation of ceramides in PC12W cells
Author(s) -
Gallinat Stefan,
Busche Silke,
Schütze Stefan,
Krönke Martin,
Unger Thomas
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01675-5
Subject(s) - ceramide , losartan , receptor , angiotensin ii , microbiology and biotechnology , apoptosis , signal transduction , receptor antagonist , sphingomyelin , chemistry , stimulation , antagonist , angiotensin receptor , endocrinology , medicine , biology , biochemistry , membrane
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.