THE RELEASE OF GLUTAMATE AND ASPARTATE FROM RAT-BRAIN SYNAPTOSOMES INRESPONSE TO DOMOIC ACID (AMNESIC SHELLFISH TOXIN) AND KAINIC ACID

Kainic acid is known to stimulate the release of glutamate (GLU) and a spartate (ASP) from presynaptic neurons. It has been suggested that th e enhanced release of these endogenous EAA's plays a significant role in the excitotoxic effects of KA. Domoic acid (DOM), a shellfish toxin , is structurally similar to KA, and has been shown to be 3-8 times mo re toxic than KA. In this study, effects of KA and DOM on the release of GLU and ASP from rat brain synaptosomes were investigated. Amino ac id analysis was performed by the reversed phase HPLC, following deriva tization with 9-fluorenylmethyl chloroformate (FMOC). Potassium chlori de (40 mM) was used as a positive control, and stimulated GLU release from rat brain synaptosomes in presence or absence of Ca2+. DOM enhanc ed the release of GLU, whereas KA stimulated the release of both GLU a nd ASP from synaptosomes in the presence of Ca2+. However, their poten cy to stimulate GLU and ASP release was enhanced in absence of Ca2+. T hese results indicate that different mechanisms may be involved in the release of GLU and ASP in response to DOM and KA, and that neurotrans mitter release appeared to be highly specific for these agonists. It w ould appear that DOM and KA may interact with different receptors on t he presynaptic nerve terminal, and/or activate different subtypes of v oltage-dependent Ca2+ channels to promote influx of Ca2+ which is targ eted for different pools of neurotransmitters.