ACTIVATION OF MUSCARINIC RECEPTORS INHIBITS APOPTOSIS IN PC12M1 CELLS

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.