Bilobalide, a constituent of Ginkgo biloba, inhibits NMDA-induced phospholipase A(2) activation and phospholipid breakdown in rat hippocampus

In rat hippocampal slices superfused with magnesium-free buffer, glutamate (1 mM) caused the release of large amounts of choline due to phospholipid b reakdown. This phenomenon was mimicked by N-methyl-D-aspartate (NMDA) in a calcium-sensitive manner and was blocked by NMDA receptor antagonists such as MK-801 and 7-chlorokynurenate, The NMDA-induced release of choline was n ot caused by activation of phospholipase D but was mediated by phospholipas e A(2) (PLA(2)) activation as the release of choline was accompanied by the formation of lyso-phosphatidylcholine (lyso-PC) and glycerophospho-choline (GPCh) and was blocked by 5-[2-(2-carboxyethyl) -4-dodecanoyl-3,5-dimethyl pyrrol-1-yl]pentanoic acid, a PLA(2) inhibitor. Bilobalide, a constituent o f Ginkgo biloba, inhibited the NMDA-induced efflux of choline with an IC50 value of 2.3 mu M and also prevented the formation of lyse-PC and GPCh. NMD A also caused a release of choline in vivo when infused into the hippocampu s of freely moving rats by retrograde dialysis. Again, the effect was compl etely inhibited by bilobalide which was administered systemically (20 mg/kg i.p.). Interestingly, convulsions which were observed in the NMDA-treated rats were almost totally suppressed by bilobalide. We conclude that release of choline is a sensitive marker for NMDA-induced phospholipase A(2) activ ation and phospholipid breakdown. Bilobalide inhibited the glutamatergic ex citotoxic membrane breakdown both in vitro and in vivo, an effect which may be beneficial in the treatment of brain hypoxia and/or neuronal hyperactiv ity.