Vigabatrin enhances promoted release of GABA in neonatal rat optic nerve.
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.
Yee
J M
JM
Department of Neurology, Yale University School of Medicine and Neuroscience Research Center, VA Medical Center, West Haven, CT 06516, USA.
Agulian
S
S
Kocsis
J D
JD
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008959:Models, Neurological; D009557:Nipecotic Acids / Q000494:pharmacology*; D009900:Optic Nerve / Q000187:drug effects / Q000502:physiology*; D027361:Organic Anion Transporters; D011189:Potassium Chloride / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D000927:Anticonvulsants; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D011963:Receptors, GABA-A; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D011392:Proline; C010983:homoproline; D020888:Vigabatrin; D001640:Bicuculline