Effect of ginkgolides on beta-amyloid-suppressed acetylocholine release from rat hippocampal slices

As Ginkgo has been shown to improve age‐related memory deficits and β‐amyloid‐related peptides have been suggested to play a significant role in memory degeneration in Alzheimer's disease, the present study was carried out to examine the effect of two major ginkgolides, A and B, on β‐amyloid peptide‐modulated acetylcholine (ACh) release from hippocampal brain slices. Addition of β‐amyloid fragment25–35 (0.01–1 µM) in the superfusion medium suppressed the K+‐evoked [3H]‐ACh release from the rat hippocampal slices in a concentration‐related manner; a 40% reduction in ACh outflow was observed with the highest amyloid concentration used (1 µM). Inclusion of ginkgolide B (GKB, 0.01–10 µM) caused a concentration‐related reversion of the inhibitory effect elicited by the effective concentration of β‐amyloid (1 µM). The reversal of the β‐amyloid‐inhibited ACh release by GKB (1 µM) was not blocked by tetrodotoxin (1 µM) indicating a direct interaction of GKB on the cholinergic nerve terminals. In contrast, addition of the same concentration range of ginkgolide A (GKA, 0.01–10 µM) had no effect on β‐amyloid‐inhibited ACh release. These results suggest that GKB may elicit its anti‐amnesic effect by minimizing the inhibitory effect of β‐amyloid peptides on cholinergic transmission. Copyright © 2004 John Wiley & Sons, Ltd.