Role of CREB in the regulatory action of sarsasapogenin on muscarinic M1 receptor density during cell aging

This work studied the role of cyclic AMP responsive element binding protein (CREB) in the up-regulation of M1 muscarinic acetylcholine receptor (M1 receptor) density by sarsasapogenin (ZMS) in CHO cells transfected with M1 receptor gene (CHOm1 cells). During cell aging, sarsasapogenin elevated M1 receptor density as well as CREB and phosphor-CREB (pCREB) levels. CREB peaked earliest, followed by pCREB and M1 receptor density peaked last. When CREB synthesis was blocked by antisense oligonucleotides, the elevation effect of sarsasapogenin on M1 receptor density was abolished. These results suggest that sarsasapogenin up-regulates M1 receptor density in aged cells by promoting CREB production and phosphorylation. Furthermore, the results support the hypothesis that pCREB regulates M1 receptor gene expression through heterodimer formation.