Effects of the nerve agents soman and tabun on the uptake and release of GABA and glutamate in synaptosomes of guinea pig cerebral cortex.
1. Crude and purified synaptosomes were prepared from the cerebral cortex of the rat or the guinea pig and used to study the uptake and release of [3H]GABA and [3H]glutamate. 2. Baclofen at 10(-5) M inhibited stimulated release of [3H]GABA from crude rat and guinea pig synaptosomes, but not from purified rat synaptosomes. 3. 1-2 mM tabun decreased the uptake of [3H]GABA and increased the uptake of [3H]glutamate by purified guinea pig synaptosomes. 4. Soman and tabun at 10(-6) M and 10(-5) M inhibited basal release of [3H]GABA and [3H]glutamate from crude guinea pig synaptosomes. Tabun at 10(-5) M decreased stimulated release of [3H]GABA while soman had no effect. 5. The results do not sustain the possibility that nerve agents cause convulsions by affecting the uptake or release of GABA or glutamate. However indirect evidence was obtained that soman and tabun inhibit catabolism of GABA and glutamate.
Szilagyi
M
M
DSTO, Materials Research Laboratory, Melbourne, Australia.
Gray
P J
PJ
Dawson
R M
RM
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism; D010755:Organophosphates / Q000494:pharmacology*; D051381:Rats; D012999:Soman / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D005971:Glutamates; D018377:Neurotransmitter Agents; D010755:Organophosphates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D012999:Soman; D001418:Baclofen; C009374:tabun