Stimulation of alpha4beta2 nicotinic acetylcholine receptors inhibits beta-amyloid toxicity.
We examined the effects of nicotinic receptor agonists against beta amyloid (Abeta) cytotoxicity to rat cortical neurons. Administration of nicotine protected against Abeta-induced neuronal death. This neuroprotection was blocked by dihydro-beta-erythroidine, an alpha4beta2 nicotinic receptor antagonist. Furthermore, incubation with cytisine, a selective alpha4beta2 nicotinic receptor agonist, inhibited Abeta cytotoxicity. These results suggest that alpha4beta2 nicotinic receptor activation plays an important role in neuroprotection against Abeta cytotoxicity.
Kihara
T
T
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.
Shimohama
S
S
Urushitani
M
M
Sawada
H
H
Kimura
J
J
Kume
T
T
Maeda
T
T
Akaike
A
A
D000470:Alkaloids / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001392:Azocines; D002038:Bungarotoxins / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D009474:Neurons / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011807:Quinolizines; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D001392:Azocines; D002038:Bungarotoxins; D004079:Dihydro-beta-Erythroidine; D018696:Neuroprotective Agents; D009538:Nicotine; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids