Influence of gamma-aminobutyric acid on retinal cells excitotoxicity upon glucose deprivation.
The role of extracellular endogenous gamma-aminobutyric acid (GABA) in rescuing retinal cells in culture from the decrease in viability induced by Glu under metabolic inhibition is analyzed. Glutamate (10 microM-10 mM) dose-dependently decreased the intracellular GABA content, but increased the extracellular accumulation of GABA. In the absence of glucose, Glu (10-100 microM) decreased the intracellular GABA (2-fold), whereas the extracellular accumulation of GABA was increased by about 4-fold. Glu-mediated decrement in cell survival was not affected by inhibiting the GABA(A) receptors with bicuculline (1 or 10 microM) or by blocking the Na+ -dependent release of GABA with 1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (SKF89976-A). Data suggest a non-protective role of endogenous GABA release after metabolic deprivation of retinal cells submitted to Glu.
Center for Neuroscience of Coimbra and Faculty of Medicine, University of Coimbra, Portugal.
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D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D004396:Coloring Agents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018682:GABA Agents / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009557:Nipecotic Acids / Q000494:pharmacology; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D004396:Coloring Agents; D018682:GABA Agents; D018756:GABA Antagonists; D009557:Nipecotic Acids; D013778:Tetrazolium Salts; D013844:Thiazoles; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; C022616:thiazolyl blue; D005947:Glucose; D001640:Bicuculline