Domoic acid induces the release of glutamate in the rat hippocampal CA3 sub-region

WE investigated the role of kainate receptor activation in modulating the influx of Ca2+ coupled to the exocytotic release of glutamate in rat hippocampal synaptosomal fractions (P2). In whole hippocampus synaptosomes stimulation with domoic acid increased the intracellular free Ca2+ concentration ([Ca2+](i)) in a dose-dependent manner with an EC(50) of 0.16 mu M, whereas the EC(50) for kainate was 0.86 mu M and for (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isosazolepropionic acid (AMPA) was 43.04 mu M. Stimulation of the synaptosomes with 10 mu M domoic acid induced Ca2+-dependent release of endogenous glutamate. Also, in synaptosomes isolated from the CA3 subregion of the hippocampus the domoic acid-induced release of glutamate was higher than that from the dentate gyrus (221.3%), from the CA1 (188.1%) or from the whole hippocampal synaptosomes (131.5%). These results support the existence of a presynaptic kainate receptor which may control the exocytotic release of glutamate in the CA3 sub-region of the rat hippocampus.