Beta-amyloid peptides inhibit acetylcholine release from cholinergic presynaptic nerve endings isolated from an electric ray.
We investigated the effects of beta-amyloid (Abeta) peptides on cholinergic synaptosomes isolated from the electric organ of the Japanese marine ray Narke japonica. Fresh and pre-incubated solutions of Abeta(1-42) inhibited acetylcholine (ACh) release from the synaptosomes evoked by high [K+] depolarization when incubated with synaptosomes for 10 min before the depolarizing stimulus. A freshly prepared solution of Abeta(1-40) did not inhibit the evoked ACh release, but prolonged pre-incubation of Abeta(1-40) solution caused the inhibition. Abeta(1-15) neither in fresh nor pre-incubated solution inhibited. These results have demonstrated that Abeta peptides can acutely inhibit the depolarization-evoked release of ACh by acting directly on cholinergic presynaptic nerve endings. The electrophoresis analysis showed a strong correlation between Abeta aggregation and its inhibition for ACh release.
Satoh
Y
Y
Laboratory of Neurobiophysics, School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
Hirakura
Y
Y
Shibayama
S
S
Hirashima
N
N
Suzuki
T
T
Kirino
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012860:Skates, Fish / Q000033:anatomy & histology / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000109:Acetylcholine