Abstract
Vigabatrin (gamma-vinyl GABA) is an antiepileptic drug and blocks GABA transaminase activity resulting in elevations in cellular GABA levels in the brain. Nipecotic acid (NPA) promotes release of GABA from neonatal optic nerve astrocytes, resulting in a bicuculline-sensitive depolarization of the optic nerve axons. The NPA-induced depolarization of vigabatrin-treated rats (100 mg/kg, i.p.) more than doubled, suggesting an elevation in free GABA levels; the GABA transporter inhibitor, NO-711 reduced the depolarization. These results are consistent with the known ability of vigabatrin to block the GABA degradation enzyme GABA-transaminase, suggesting that vigabatrin elevates astrocytic GABA levels, thereby favoring greater release of GABA through the GABA transporter.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Anticonvulsants / pharmacology*
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Astrocytes / drug effects
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Astrocytes / physiology*
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Axons / physiology
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Bicuculline / pharmacology
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Carrier Proteins / metabolism
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GABA Plasma Membrane Transport Proteins
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In Vitro Techniques
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Proteins / metabolism
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Membrane Transport Proteins*
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Models, Neurological
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Nipecotic Acids / pharmacology*
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Optic Nerve / drug effects
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Optic Nerve / physiology*
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Organic Anion Transporters*
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Potassium Chloride / pharmacology
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Proline* / analogs & derivatives*
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Rats
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Rats, Wistar
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Receptors, GABA-A / drug effects
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Receptors, GABA-A / physiology
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Time Factors
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Vigabatrin
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gamma-Aminobutyric Acid / analogs & derivatives*
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gamma-Aminobutyric Acid / metabolism*
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gamma-Aminobutyric Acid / pharmacology
Substances
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Anticonvulsants
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Carrier Proteins
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GABA Plasma Membrane Transport Proteins
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Membrane Proteins
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Membrane Transport Proteins
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Nipecotic Acids
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Organic Anion Transporters
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Receptors, GABA-A
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nipecotic acid
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gamma-Aminobutyric Acid
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Potassium Chloride
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Proline
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homoproline
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Vigabatrin
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Bicuculline