GABA and benzodiazepine-induced modification of [14C]L-glutamic acid release from rat spinal cord slices.
The spontaneous and potassium-evoked release of [14C]-label from rat spinal cord slices preloaded with [14C]L-glutamic acid and its modification by GABA and related drugs, such as flurazepam, was studied as a possible indirect measure of presynaptic inhibition and of the ability of benzodiazepines to augment it. GABA (100 microM) reduced the spontaneous release of [14C]-label (glutamate) provided that GABA metabolism was blocked by amino-oxyacetic acid (AOAA), but failed to reduce the potassium-evoked release of glutamate, although muscimol (10 microM) had some effect. In contrast, flurazepam (1-100 microM) did not affect spontaneous release but produced some inhibition of the evoked release (through a system insensitive to 10 microM bicuculline). This inhibition became more marked in the presence of both GABA and AOAA, and was then overcome by bicuculline. It is concluded that either some benzodiazepine receptors must be occupied for GABA to produce an effect on evoked release and/or, that the benzodiazepines can only augment GABA function once a certain amount has been released. Studies of the rapid distribution of [14C]-label from glutamate, to GABA, glutamine and other amino acids, using high voltage electrophoresis, showed the importance of blocking metabolic pathways in studies of this kind.
Vellucci
S V
SV
Webster
R A
RA
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004347:Drug Interactions; D005479:Flurazepam / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000502:physiology
D005971:Glutamates; D000625:Aminooxyacetic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005479:Flurazepam; D011188:Potassium; D001640:Bicuculline