NGF-DEPENDENT NEUROTROPHIC-LIKE EFFECTS OF AF102B, AN M1 MUSCARINIC AGONIST, IN PC12M1 CELLS

THE non-selective muscarinic agonist oxotremorine induces atropine-sen sitive neurite outgrowth in PC12 cells stably transfected with mi musc arinic receptors. In contrast, AF102B, an M1-selective muscarinic agon ist, mediated minimal neurite outgrowth in these cells. In the presenc e of nerve growth factor (NGF) however, it induced atropine-sensitive neurite outgrowth in almost half the cell population. AF102B mediated phosphoinositide hydrolysis, but unlike carbachol, it did not stimulat e cyclic AMP accumulation in these cells. These signals were not affec ted by NGF, indicating that they were not directly responsible for the cholinergic neurotrophic-like response. Our observations suggest that AF102B may improve neuronal responsiveness to neurotrophic factors, a nd thus may provide another beneficial aspect for treating Alzheimer's disease.