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.