beta-amyloid peptides inhibit acetylcholine release from cholinergic presynaptic nerve endings isolated from an electric ray

We investigated the effects of beta -amyloid (A beta) peptides on cholinerg ic synaptosomes isolated from the electric organ of the Japanese marine ray Narke japonica. Fresh and pre-incubated solutions of A beta (1-42) inhibit ed acetylcholine (ACh) release from the synaptosomes evoked by high [Kt] de polarization when incubated with synaptosomes for 10 min before the depolar izing stimulus. A freshly prepared solution of A beta (1-40) did not inhibi t the evoked ACh release, but prolonged pre-incubation of A beta (1-40) sol ution caused the inhibition. A beta (1-15) neither in fresh nor pre-incubat ed solution inhibited. These results have demonstrated that A beta peptides can acutely inhibit the depolarization-evoked release of ACh by acting dir ectly on cholinergic presynaptic nerve endings. The electrophoresis analysi s showed a strong correlation between A beta aggregation and its inhibition for ACh release. (C) 2001 Elsevier Science Ireland Ltd. All rights reserve d.