Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by donepezil: role of sigma-1 receptors and IP3 receptors.
In addition to acetylcholinesterase (AChE) inhibition, donepezil binds to sigma-1 receptors. In this study, we examined the effects of donepezil on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Donepezil significantly potentiated the NGF-induced neurite outgrowth in a concentration-dependent manner whereas the AChE inhibitor physostigmine did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth by donepezil was significantly blocked by co-administration of the selective sigma-1 receptor antagonist NE-100 or the inositol 1,4,5-triphosphate (IP3) receptor antagonist xestospongin C. These findings suggest that sigma-1 receptors and interaction with IP3 receptors may be involved in the pharmacological action of donepezil.
Ishima
Tamaki
T
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Department of Psychiatry, Chiba University School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Nishimura
Tomoko
T
Iyo
Masaomi
M
Hashimoto
Kenji
K
D000704:Analysis of Variance; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007189:Indans / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D010080:Oxazoles / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology*; D000097605:Sigma-1 Receptor
D000840:Anisoles; D002800:Cholinesterase Inhibitors; D000077265:Donepezil; D007189:Indans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D008869:Microtubule-Associated Proteins; D020932:Nerve Growth Factor; D010080:Oxazoles; D010830:Physostigmine; D010880:Piperidines; D011437:Propylamines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C511704:xestospongin C; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride