Ginkgo Biloba Research Today is a free monthly online journal that collates and summarizes the latest research about Ginkgo Biloba, including details on ginkgo biloba, herbal remedies, side effects, benefits. | ||||||||
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Role of GABAergic antagonism in the neuroprotective effects of bilobalide.Kiewert C, Kumar V, Hildmann O, Rueda M, Hartmann J, Naik RS, Klein J Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, 1300 Coulter Dr., Amarillo, TX 79106, USA. Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to block GABA(A) receptors. The goal of this study was to test the potential role of a GABAergic mechanism for the neuroprotective activity of bilobalide. In rat hippocampal slices exposed to NMDA, release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 muM) and under low-chloride conditions. Bicuculline (100 muM), a competitive antagonist at GABA(A) receptors, reduced NMDA-induced choline release to a small extent (-23%). GABA (100 muM) partially antagonized the inhibitory action of bilobalide. Exposure of hippocampal slices to NMDA also caused edema formation as measured by increases of tissue water content. NMDA-induced edema formation was suppressed by bilobalide and by low-chloride conditions. Bicuculline exerted partial protection (by 30%) while GABA reduced bilobalide's effect by about one third. To investigate bilobalide's interaction with GABA(A) receptors directly, we measured binding of [(35)S]-TBPS to rat cortical membranes. TBPS binding was competitively inhibited by bilobalide in the low micromolar range (IC(50)=3.7 muM). As a functional test, we determined (36)chloride flux in rat corticohippocampal synaptoneurosomes. GABA (100 muM) significantly increased (36)chloride flux (+65%), and this increase was blocked by bilobalide, but with low potency (IC(50): 39 muM). We conclude that, while antagonism of GABA(A) receptors may contribute to bilobalide's neuroprotective effects, additional mechanisms must be postulated to fully explain bilobalide's actions. Published 12 January 2007 in Brain Res, 1128(1): 70-8.
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