Effects of kainic and domoic acids on the release of glutamate and aspartate from rat brain synaptosomes

It has been proposed that domoic acid (DOM) and kainic acid (KA) produce neurotoxicity by acting at excitatory amino acid (EAA) receptors, causing a prolonged depolarization which results in death of the postsynaptic neuron. In this work, the effects of KA and DOM on the release of glutamate (GLU) and aspartate (ASP) from isolated presynaptic nerve terminals (synaptosomes) were compared. Responses to KA and DOM were similar. Concentrations of 0.5 and 1.0mM KA and DOM increased GLU release (p $\le$ 0.01), however only 1.0mM KA produced a significant increase in ASP release (p $\le$ 0.05). The calcium dependence of these effects was examined by comparing the effects of 1mM KA and DOM in the presence and absence of calcium. Calcium free media contained 1mM EGTA. It was found that amino acid release stimulated by KA and DOM was calcium independent. Potassium-stimulated GLU and ASP release were also calcium independent in this preparation. Results indicate that GLU and ASP release stimulated by KA and DOM originate from cytoplasmic stores, and may be released by reversal of the acidic amino acid uptake carrier. The high concentrations of agonist required to stimulate release, and similar potencies of KA and DOM suggest that this effect is not of primary importance to the neurotoxic mechanism of these compounds. (Abstract shortened by UMI.).