Domoic acid induces the release of glutamate in the rat hippocampal CA3 subregion.
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 EC50 of 0.16 microM, whereas the EC50 for kainate was 0.86 microM and for (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) was 43.04 microM. Stimulation of the synaptosomes with 10 microM domoic acid induced Ca(2+)-dependent release of endogenous glutamate. Also, in synaptosomes isolated from the CA3 sub-region 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.
Malva
J O
JO
Centre for Neuroscience of Coimbra, Department of Zoology, University of Coimbra, Portugal.
Carvalho
A P
AP
Carvalho
C M
CM
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000819:agonists*; D017661:Receptors, Presynaptic / Q000819:agonists*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D017661:Receptors, Presynaptic; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C012301:domoic acid