Role of GABAergic antagonism in the neuroprotective effects of bilobalide.

Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Research Abstract Details 

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Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Abstract Text:

Cornelia Kiewert,Vikas Kumar,Oksana Hildmann,Misty Rueda,Joachim Hartmann,Runa S Naik,Jochen Klein,

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 microM) and under low-chloride conditions. Bicuculline (100 microM), a competitive antagonist at GABA(A) receptors, reduced NMDA-induced choline release to a small extent (-23%). GABA (100 microM) 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 microM). As a functional test, we determined (36)chloride flux in rat corticohippocampal synaptoneurosomes. GABA (100 microM) significantly increased (36)chloride flux (+65%), and this increase was blocked by bilobalide, but with low potency (IC(50): 39 microM). 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.

Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Publishing Authors By Initials

C Kiewert,V Kumar,O Hildmann,M Rueda,J Hartmann,RS Naik,J Klein,

For similar organic chemicals: carboxylic acids: acids, acyclic: butyric acids: aminobutyric acids: gamma-aminobutyric acid research abstracts see: organic chemicals: carboxylic acids: acids, acyclic: butyric acids: aminobutyric acids: gamma-aminobutyric acid research

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Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Brain research

VOLUME: 1128

Page Numbers: 70-8

Journal Abbreviation: Brain Res.

ISSN: 0006-8993

DAY: 28

MONTH: 11

YEAR: 2006

Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 45503

Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Keywords Mesh Terms:

KEYWORDS: gamma-Aminobutyric Acid

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Role of GABAergic antagonism in the neuroprotective effects of bilobalide. Information

Substance Name: tert-butylbicyclophosphorothionate

Registry Number: 70636-86-1

Grant and Affiliation Information for Role of GABAergic antagonism in the neuroprotective effects of bilobalide.

AFFILIATION: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, 1300 Coulter Dr., Amarillo, TX 79106, USA.

Country: Netherlands

AGENCY: United States NCCAM

GRANT: R21 AT003399-01A1

ACRONYM: AT

MEDLINETA: Brain Res

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