Energy utilization in the induced release of gamma-aminobutyric acid from synaptosomes.
Newly accumulated gamma-aminobutyric acid (GABA) was released from synaptosomes by treatment with 30 mM K+ or the Ca2+ ionophore A23187. Release was Ca2+-dependent and energy-dependent. The induced release of GABA was inhibited by S-13, an uncoupler of oxidative phosphorylation, by azide, a blocker of mitochondrial respiration, and by oligomycin, efrapeptin, tributyltin and dicyclohexylcarbodiimide (DCCD), which are inhibitors of Ca2+/Mg2+-ATPases, including mitochondrial ATPase. Efrapeptin blocked GABA release induced by K+ but not A23187-induced release. Azide and oligomycin appeared to inhibit GABA release as a consequence of their effects on mitochondrial ATP synthesis. However, the inhibition of GABA release by the other compounds could not be totally accounted for by their effects on synaptosomal ATP stores. It is proposed that these compounds, in addition to affecting ATP synthesis, directly affect biochemical reactions involved in GABA release. Thus, these and similar inhibitors seem to be useful probes of the transmitter release process.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists; D005711:Gallopamil / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D018756:GABA Antagonists; D000001:Calcimycin; D005711:Gallopamil; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D012964:Sodium; D011188:Potassium; D002118:Calcium