Domoic acid induced release of [3H]GABA in cultured chick retina cells.
The effect of the neurotoxin domoic acid (DOM), a structural analogue of kainic acid, on the release of [3H]gamma-aminobutyric acid (GABA) and on the [Ca2+]i was studied in cultured chick retina cells. DOM stimulated dose-dependently the release of [3H]GABA with an EC50 of 2.5 microM. In Ca(2+)-containing medium (1 mM), DOM (5 microM) increased the [Ca2+]i by about 190 nM and evoked the release of 11.8 +/- 1.3% of the intracellular [3H]GABA, while in the absence of extracellular Ca2+ DOM induced the release of only 7.9 +/- 1.4% of the accumulated [3H]GABA. The Ca(2+)-independent release of [3H]GABA was blocked by the non-competitive inhibitor of the GABA carrier 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3-py ridine- carboxylic acid hydrochloride (NNC-711), but a component of Ca(2+)-dependent release remains. DOM evoked Ca(2+)-independent release of [3H]GABA was significantly depressed in the absence of external Na+ and completely blocked by the non-selective antagonist of the non-NMDA glutamate receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Similarly, CNQX decreased the [Ca2+]i response to DOM, whereas L(+)-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist of the metabotropic glutamate receptors, was without effect. MK-801 did not affect the release of [3H]GABA stimulated by DOM. Taken together our results indicate that DOM evokes both Ca(2+)-dependent and Ca(2+)-independent release of [3H]GABA, most likely by activating kainate receptors.
Alfonso
M
M
Department of Fundamental Biology, University of Vigo, Spain.
Duran
R
R
Duarte
C B
CB
Ferreira
I L
IL
Carvalho
A P
AP
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D009498:Neurotoxins; D009539:Nicotinic Acids / Q000494:pharmacology; D009557:Nipecotic Acids; D010091:Oximes / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009498:Neurotoxins; D009539:Nicotinic Acids; D009557:Nipecotic Acids; D010091:Oximes; D011810:Quinoxalines; C078793:NNC 711; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C012301:domoic acid; D007608:Kainic Acid; D002118:Calcium