The inhibitory and facilitatory actions of amyloid-beta peptides on nicotinic ACh receptors and AMPA receptors.
The present study investigated the effects of amyloid-beta peptides on nicotinic ACh receptors (Torpedo, alpha 4 beta 2, and alpha 7 receptors) and AMPA receptors expressed in Xenopus oocytes by monitoring whole-cell membrane currents. Ten-minutes treatment with amyloid-beta(1-42) (1 microM) inhibited Torpedo ACh receptor currents, reaching 53% of original levels 30 min after treatment. Amyloid-beta(1-40) inhibited the currents in a dose-dependent manner (0.1-10 microM) during treatment, gradually reversing after treatment. Amyloid-beta(1-40) and amyloid-beta(1-42) (0.1 microM) depressed alpha 4 beta 2 receptor currents to each 69% and 62% of original levels at 10-min treatment and lesser depression was obtained with alpha 7 receptors. Amyloid-beta(1-42) (0.1 microM) did not significantly inhibit AMPA receptor currents, but amyloid-beta(1-40) (0.1 microM) potentiated the currents to 145-191% of original levels. Amyloid-beta peptides, thus, exert their diverse actions on nicotinic ACh receptors and AMPA receptors, and the inhibitory actions on nicotinic ACh receptors may account for the deterioration of learning and memory in Alzheimer's disease.
Tozaki
Hidetoshi
H
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya-shi 663-8501, Japan.
Matsumoto
Akira
A
Kanno
Takeshi
T
Nagai
Kaoru
K
Nagata
Tetsu
T
Yamamoto
Satoshi
S
Nishizaki
Tomoykui
T
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014101:Torpedo; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018091:Receptors, AMPA; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C403531:nicotinic receptor alpha4beta2