Involvement of M1-muscarinic acetylcholine receptors, protein kinase C and mitogen-activated protein kinase in the effect of huperzine A on secretory amyloid precursor protein-alpha.
This study is to explore the involvement of muscarinic acetylcholine receptors/protein kinase C cascade and the mitogen-activated protein kinase pathway in the effect of huperzine A on the secretory amyloid precursor protein-alpha. Upregulation of secretory amyloid precursor protein-alpha by huperzine A was attenuated by muscarinic acetylcholine receptor antagonist (specifically by M1-muscarinic acetylcholine receptor antagonist), and markedly blocked (-37.7%) by protein kinase C inhibitor as well. Meanwhile, huperzine A can activate the phosphorylation of mitogen-activated protein kinase and, accordingly, partly restored PD98059-decreased secretory amyloid precursor protein-alpha secretion. In addition, huperzine A largely inhibited (-55.4%) acetylcholinesterase activity of the cell line. Our results suggest that activated M1-muscarinic acetylcholine receptor/protein kinase C pathway and mitogen-activated protein kinase signaling are involved in the process of huperzine A enhancing the secretory amyloid precursor protein-alpha secretion.
Yan
Han
H
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zhang
Hai Yan
HY
Tang
Xi Can
XC
D000470:Alkaloids; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008464:Mecamylamine / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000187:drug effects* / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015854:Up-Regulation
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D043643:Receptor, Muscarinic M1; D000685:Serum Amyloid A Protein; D012717:Sesquiterpenes; C050426:huperzine A; D008464:Mecamylamine; D012601:Scopolamine; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases