gamma-Aminobutyric acid (GABA) enhances glutamate cytotoxicity in a cerebellar cell line.
A temperature-sensitive rat cerebellar cell line SC9 has been used to study the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in glutamate cytotoxicity. GABA increases glutamate toxicity in a dose-dependent fashion, but NMDA and kainic acid were not toxic in the presence or absence of GABA. The specificity of this cytotoxicity was further indicated by the NMDA-selective antagonist 2-amino-7-phosphonoheptanoic acid (APV), which does not block glutamate effect. These observations, as well as binding experiments with 3H-glutamate, suggest that glutamate cytotoxicity in these cells depends on quisqualate-selective uptake sites of the amino acid. The study may open therefore a novel pathway for understanding the cytotoxic effect of excitatory amino acids in brain structures that are enriched with GABA and glutamate uptake sites.
Simantov
R
R
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005971:Glutamates; D009498:Neurotoxins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007770:L-Lactate Dehydrogenase