title: Activation of muscarinic acetylcholine receptors inhibits cell cycle progression of small cell lung carcinoma.
abstract: We previously reported that activation of muscarinic acetylcholine receptors (mAChR) of M3 subtype causes hydrolysis of phosphoinositides and inhibits voltage-gated Ca2+ channel activity in small cell lung carcinoma (SCLC) cells. We now report that mAChR activation causes exponentially growing SCLC cells to arrest in S and G2/M phases of the cell cycle, concomitant with a decrease in DNA synthesis. Cell cycle progression and DNA synthesis resume when mAChR are down-regulated. In serum-starved SCLC cells, mAChR activation inhibits DNA synthesis induced by serum, bombesin, insulin, or insulin-like growth factor-I. The finding that DNA synthesis is inhibited even when mAChR are activated after exposure of cells to growth factors indicates that decreased signal transduction by growth factor receptors is not the mechanism of mAChR-mediated growth inhibition. Our data suggest that mAChR activation disrupts a common event that is induced by different growth factors and is fundamental for cell cycle progression.
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
authors.forename: C L
authors.initials: CL
authors.lastname: Williams
authors.forename: V A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018288:Carcinoma, Small Cell; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D007328:Insulin; D011950:Receptors, Cholinergic; D007334:Insulin-Like Growth Factor I; D002217:Carbachol; D004247:DNA; D001839:Bombesin; D002118:Calcium