title: Nicotinic receptor-dependent and -independent effects of galantamine, an acetylcholinesterase inhibitor, on the non-neuronal acetylcholine system in C2C12 cells.
abstract: We previously reported that satellite cells possess the ability to produce angiogenic factors, including fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF) in vivo. However, whether C2C12 cells possess a non-neuronal cholinergic system (NNCS) or non-neuronal ACh (NNA) remains to be studied; therefore, we investigated the system using C2C12 cells and its regulatory mechanisms. C2C12 cells synthesized ACh, the level of which was comparable with that of cardiomyocytes, and the synthesis was augmented by the acetylcholinesterase inhibitor galantamine. The ChAT promoter activity was upregulated by nicotine or galantamine, partly through nicotinic receptors for both agents as well as through a non-nicotinic receptor pathway for galantamine. Further, VEGF secretion by C2C12 cells was also increased by nicotine or galantamine through nicotinic receptors as well as partly through non-nicotinic pathways in the case of galantamine. These results suggest that C2C12 cells are equipped with NNCS or NNA, which is positively regulated through nicotinic or non-nicotinic pathways, particularly in the case of galantamine. These results provide a novel concept that myogenic cells expressing NNA can be a therapeutic target for regulating angiogenic factor synthesis.
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Oikawa
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Mano
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Iketani
authors.affiliation: Department of Physiology, Nippon Medical School Graduate school of Medicine, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. Electronic address: k12417853@nms.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kakinuma
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005702:Galantamine / Q000494:pharmacology*; D051379:Mice; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D011978:Receptors, Nicotinic; D042461:Vascular Endothelial Growth Factor A; D005702:Galantamine; D009538:Nicotine; D000109:Acetylcholine
keywords: Acetylcholinesterase inhibitor; C2C12 cells; Galantamine; Non-neuronal acetylcholine; VEGF