Stimulation of [3H]gamma-aminobutyric acid release by calcium chelators in synaptosomes.
The effect of EGTA on the release of labeled gamma-aminobutyric acid (GABA), glutamate, acetylcholine, and dopamine was studied in superfused synaptosomes from mouse brain. In the absence of both Ca2+ and Mg2+, EGTA and also EDTA at 50 microM or higher concentrations induced a 2.5-5-fold stimulation of [3H]GABA release, similar to that produced by potassium depolarization, whereas only a slight effect, or no effect at all, was observed on the release of the other transmitters studied. The GABA-releasing action of EGTA was practically abolished in the presence of Mg2+. In contrast, the effect of EDTA was also observed when the medium contained Mg2+. Studies on the ionic dependence showed that the stimulation of GABA release by EGTA was abolished in a Na+-free medium. Li+ did not substitute Na+ for the EGTA effect, which was also independent of chloride. This Na+ dependence does not seem to involve voltage-sensitive channels, since tetrodotoxin did not affect the GABA-releasing action of EGTA, whereas in parallel superfusion chambers it blocked over 80% the stimulation of GABA release by veratridine. In contrast, two calcium channel blockers in synaptosomes, La3+ and the cationic dye ruthenium red, greatly inhibited the GABA-releasing effect of EGTA. L-2,4-Diaminobutyric acid, an inhibitor of the Na+-dependent GABA carrier, did not affect the releasing action of EGTA, whereas in a parallel experiment this drug inhibited by more than 90% the exchange of labeled GABA with unlabeled GABA.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology*; D005026:Ethylene Glycols / Q000494:pharmacology*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005026:Ethylene Glycols; D005971:Glutamates; D018698:Glutamic Acid; D013779:Tetrodotoxin; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D004492:Edetic Acid; D012964:Sodium; D008274:Magnesium; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine