Effect of ginkgolides on beta-amyloid-suppressed acetylocholine release from rat hippocampal slices.
As Ginkgo has been shown to improve age-related memory de fi cits and beta-amyloid-related peptides have been suggested to play a signi fi cant 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 beta-amyloid peptide-modulated acetylcholine (ACh) release from hippocampal brain slices. Addition of beta-amyloid fragment(25-35) (0.01-1 micro M) in the superfusion medium suppressed the K(+)-evoked [(3)H]-ACh release from the rat hippocampal slices in a concentration-related manner; a 40% reduction in ACh out fl ow was observed with the highest amyloid concentration used (1 micro M). Inclusion of ginkgolide B (GKB, 0.01-10 micro M) caused a concentration-related reversion of the inhibitory effect elicited by the effective concentration of beta-amyloid (1 micro M). The reversal of the beta-amyloid-inhibited ACh release by GKB (1 micro M) was not blocked by tetrodotoxin (1 micro M) 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 micro M) had no effect on beta-amyloid-inhibited ACh release. These results suggest that GKB may elicit its anti-amnesic effect by minimizing the inhibitory effect of beta-amyloid peptides on cholinergic transmission.
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Tze-Fun
TF
Lee
Chieh-Fu
CF
Chen
Lawrence C H
LC
Wang
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba; D046934:Ginkgolides; D006624:Hippocampus / Q000187:drug effects*; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; C045856:ginkgolide B; D000109:Acetylcholine; C477042:ginkgolide A