Previous studies have shown that PC12 cells depend on growth factors f
or their survival. When deprived of growth factors, the cells undergo
a dying process termed ''apoptosis'' (programed cell death). We show h
ere that muscarinic agonists inhibited the apoptotic death of growth f
actor-deprived PC12M1 cells (PC12 cells stably expressing cloned m1 mu
scarinic acetylcholine receptors). This protective effect of the musca
rinic agonists was observed in both proliferating and neuronal PC12M1
cells, was blocked by the muscarinic antagonist atropine, and was not
observed in PC12 cells lacking m1 receptors. Muscarinic receptors ther
efore mediate inhibition of apoptosis in these cells. In addition to i
ts effect on survival, the muscarinic agonist oxotremorine induced inh
ibition of DNA synthesis as well as growth arrest of exponentially gro
wing PC12M1 cells at the S and G(2)/M phases of the cell cycle. Muscar
inic receptors in these cells may therefore mediate inhibition of cell
cycle progression.