title: Subtypes of neuronal nicotinic acetylcholine receptors involved in nicotine-induced phosphorylation of extracellular signal-regulated protein kinase in PC12h cells.
abstract: Although many kinds of nicotinic acetylcholine receptor (nAChR) subtypes have been reported in the neuronal tissues, subtype differences in the nAChR-mediated intracellular signaling remains obscure. Using nAChR agonists and antagonists, the involvement of nAChRs in extracellular signal-regulated protein kinase (ERK) phosphorylation in PC12h cells was investigated. Cytisine and nicotine induced the phosphorylation of ERKs in a dose-dependent manner, whereas RJR-2403 had no effect. Cytisine, but not RJR-2403, also induced phosphorylation of CREB. Mecamylamine, dextromethorphan and 18-methoxycoronaridine inhibited nicotine-induced ERK phosphorylation with much higher affinity than dihydro-beta-erythroidine and alpha-conotoxin MII. These results suggest the involvement of alpha3beta4 nAChRs in ERK phosphorylation in PC12h cells.
authors.affiliation: Department of Pharmacology, Nara Medical University School of Medicine, 840 Shijo-Chou, Kashihara, Japan. hnakayam@naramed-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Koji
authors.initials: K
authors.lastname: Shimoke
authors.forename: Minoru
authors.initials: M
authors.lastname: Isosaki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Satoh
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeuchi
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D017362:Cyclic AMP Response Element-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids