Inhibition by Diazepam and γ-Aminobutyric Acid of Depolarization-Induced Release of [¹⁴C]Cysteine Sulfinate and [³H]Glutamate in Rat Hippocampal Slices.
Effects of diazepam and γ-aminobutyric acid-related compounds on the release of [¹⁴C]cysteine sulfinate and [³H]glutamate from preloaded hippocampal slices of rat brain were examined by a superfusion method. Diazepam markedly inhibited the release of cysteine sulfinate and glutamate evoked either by high K⁺ or veratridine without affecting that of other neurotransmitter candidates, e.g., γ-aminobutyric acid, acetylcholine, noradrenaline, and dopamine; IC₅₀ values for the release of cysteine sulfinate and glutamate were about 20 and 7 μM, respectively. γ-Aminobutyric acid (1 to 10 μM) and muscimol (100 μM) significantly reduced high K⁺-stimulated release of glutamate. Bicuculline, which had no effect on the release at a concentration of 50 μM by itself, antagonized the inhibitory effects of diazepam and γ-aminobutyric acid on glutamate release. Similar results were obtained with the release of cysteine sulfinate except that a high concentration (100 μM) of γ-aminobutyric acid was required for the inhibition. These results indicate the modulation by γ-aminobutyric acid innervation of the release of excitatory amino acids in rat hippocampal formation, and also suggest that some of the pharmacological effects of diazepam may be a consequence of inhibition of excitatory amino acid transmission.
D000818:Animals; D002250:Carbon Radioisotopes; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D005971:Glutamates; D018377:Neurotransmitter Agents; D014316:Tritium; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003545:Cysteine; D003975:Diazepam; C013461:cysteine sulfinic acid