Subtypes of neuronal nicotinic acetylcholine receptors involved in nicotine-induced phosphorylation of extracellular signal-regulated protein kinase in PC12h cells.
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.
Nakayama
Hitoshi
H
Department of Pharmacology, Nara Medical University School of Medicine, 840 Shijo-Chou, Kashihara, Japan. hnakayam@naramed-u.ac.jp
Shimoke
Koji
K
Isosaki
Minoru
M
Satoh
Hiroyasu
H
Yoshizumi
Masanori
M
Ikeuchi
Toshihiko
T
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
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