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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2008-3-24
pubmed:abstractText
Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to interact with neuronal transmission mediated by glutamate, gamma-aminobutyric acid (GABA) and glycine. The goal of this study was to test the interaction of bilobalide with glycine in assays of neuroprotection. In rat hippocampal slices exposed to N-methyl-D-aspartate (NMDA), release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 microM). Glycine (10-100 microM) antagonized the inhibitory action of bilobalide in this assay. In a second assay of excitotoxicity, we measured tissue water content as an indicator of cytotoxic edema formation in hippocampal slices which were exposed to NMDA. In this assay, edema formation was suppressed by bilobalide but bilobalide's action was attenuated in the presence of glycine and of D-serine (100 microM each). To investigate bilobalide's interaction with glycine receptors directly, we determined 36chloride flux in rat cortico-hippocampal synaptoneurosomes. Glycine (100 microM) was inactive in this assay indicating an absence of functional glycine-A receptors in this preparation. [3H]Glycine was used to assess binding at the glycine binding site of the NMDA receptor but bilobalide was found to be inactive in this assay. Finally, [3H]glycine release was monitored in hippocampal slices exposed to oxygen-glucose deprivation. In this model, glycine release was induced by ischemia, an effect that was strongly reduced by bilobalide. We conclude that bilobalide does not interact with glycine receptors in neurochemical assays but it significantly reduces the release of glycine under ischemic conditions. This effect likely contributes to bilobalide's neuroprotective effects in assays of excitotoxicity and ischemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides, http://linkedlifedata.com/resource/pubmed/chemical/Choline, http://linkedlifedata.com/resource/pubmed/chemical/Cyclopentanes, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Furans, http://linkedlifedata.com/resource/pubmed/chemical/Ginkgolides, http://linkedlifedata.com/resource/pubmed/chemical/Glycine, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids, http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate, http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glycine, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate, http://linkedlifedata.com/resource/pubmed/chemical/bilobalide
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
1201
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-50
pubmed:meshHeading
pubmed-meshheading:18325484-Animals, pubmed-meshheading:18325484-Binding, Competitive, pubmed-meshheading:18325484-Binding Sites, pubmed-meshheading:18325484-Brain Edema, pubmed-meshheading:18325484-Brain Ischemia, pubmed-meshheading:18325484-Chlorides, pubmed-meshheading:18325484-Choline, pubmed-meshheading:18325484-Cyclopentanes, pubmed-meshheading:18325484-Excitatory Amino Acid Agonists, pubmed-meshheading:18325484-Furans, pubmed-meshheading:18325484-Ginkgolides, pubmed-meshheading:18325484-Glycine, pubmed-meshheading:18325484-Hippocampus, pubmed-meshheading:18325484-Male, pubmed-meshheading:18325484-Membrane Lipids, pubmed-meshheading:18325484-N-Methylaspartate, pubmed-meshheading:18325484-Neuroprotective Agents, pubmed-meshheading:18325484-Organ Culture Techniques, pubmed-meshheading:18325484-Radioligand Assay, pubmed-meshheading:18325484-Rats, pubmed-meshheading:18325484-Rats, Sprague-Dawley, pubmed-meshheading:18325484-Receptors, Glycine, pubmed-meshheading:18325484-Receptors, N-Methyl-D-Aspartate
pubmed:year
2008
pubmed:articleTitle
Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, 1300 Coulter Dr, Amarillo, TX 79106, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't