GENE-TRANSCRIPTION OF ANGIOTENSIN-II TYPE-2 RECEPTOR IS REPRESSED BY GROWTH-FACTORS AND GLUCOCORTICOIDS IN PC12 CELLS

The mt angiotensin II type 2 receptor (AT2-R) expression was markedly downregulated by the mitogenic action of serum, growth factors and dexamethasone. The regulation by serum or growth factors did not affect the AT2-R mRNA half-life (18 h), whereas the AT2-R half-lives of dexamethasone-treated cells and proliferating cells decreased to 10 h and 15 h, respectively. Nuclear run-off assays indicated the mechanism of repression of AT2-R expression by serum, growth factors and dexamethasone or in proliferating cells to be, in large part, transcriptional. These findings indicate that transcription of the AT2-R gene is regulated in a growth state-dependent manner and suggest that this regulation provides a means by which cells can modulate their responsiveness to the actions of angiotensin II mediated through AT2-R. (C) 1995 Academic Press, Inc.