Neurotransmitter amino acids in the CNS. II. Some changes in amino acid levels in rat brain synaptosomes during and after in vitro anoxia and simulated ischemia.
The effects of in vitro anoxia and membrane depolarization by veratridine on the uptake and release of amino acids were investigated in suspensions of synaptosomes isolated from the forebrains of rats. It was observed that GABA, aspartate and glutamate were released from synaptosomes in anaerobic conditions and upon addition of veratridine in a time-dependent manner. The release of the two latter amino acids was faster and more pronounced than that of GABA. The other amino acids were not affected in any systematic way by either condition. Re-introduction of oxygen or addition of tetrodotoxin to veratridine-treated synaptosomes resulted in the re-uptake of GABA, aspartate and glutamate, which was much faster and more complete for GABA than for the acidic amino acids, especially at acid pH values. The amounts of aspartate and glutamate in the incubation mixture remained constant during all the manipulations whereas that of GABA increased by about 30% during anaerobiosis, in agreement with the results obtained during in vivo ischemia. It is postulated that synaptosomes which utilize glutamate and aspartate as neurotransmitters are more damaged by anoxia and depolarization with veratridine than the population which utilizes GABA. These observations may explain reports that those neurons which are thought to receive major glutamatergic input are particularly sensitive to the lack of oxygen.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D046508:Culture Techniques; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006863:Hydrogen-Ion Concentration; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D014701:Veratridine