Mitogen-Activated Protein Kinase-Dependent and Protein Kinase C-Dependent Pathways Link the m1 Muscarinic Receptor to β-Amyloid Precursor Protein Secretion

摘要: Full and functionally selective M1 muscarinic agonists (carbachol AF102B, respectively) activate secretion of the soluble form amyloid precursor protein (APPs) in PC12 cells expressing m1 receptor (PC12M1 cells). This activation is further augmented by neurotrophins such as nerve growth factor basic fibroblast factor. Muscarinic stimulation activates two transduction pathways that lead to APPs secretion: kinase C (PKC)-dependent mitogen-activated (MAPK)-dependent pathways. These operate parallel converge with neurotrophins, resulting enhancement when both agonist stimulate PC12M1 cells. conclusions are supported following findings: (a) Only partial blockade observed PKC, p21ras, or MAPK fully inhibited their respective specific inhibitors, GF109203X, S-trans, trans-farnesylthiosalicylic acid, PD98059. (b) K252a, which blocks PKC phorbol 12-myristate 13-acetate-induced secretion, enhances muscarinic-stimulated secretion. (c) Activation Ras-dependent but PKC-independent enhanced synergistically neurotrophins. results suggest mediated at least independent enhance signal for convergence point.