Presynaptic kainate receptors modulating glutamatergic transmission in the rat hippocampus are inhibited by arachidonic acid

Kainate receptors are ionotropic glutamate receptors located postsynaptically, mediating frequency-dependent transmission, and presynaptically, modulating transmitter release. In contrast to the excitatory postsynaptic kainate receptors, presynaptic kainate receptor can also be inhibitory and their effects may involve a metabotropic action. Arachidonic acid (AA) modulates most ionotropic receptors, in particular postsynaptic kainate receptor-mediated currents. To further explore differences between pre- and postsynaptic kainate receptors, we tested ;if presynaptic kainate receptors are affected by AA. Kainate (0.3-3 muM) and the kainate receptor agonist, domoate (60-300 nM), inhibited by 19-54% the field excitatory postsynaptic potential (fEPSP) slope in rat CA1 hippocampus, and increased by 12-32% paired-pulse facilitation (PPF). AA (10 muM) attenuated by 37-72% and by 62-66% the domoate (60-300 nM)-induced fEPSP inhibition and paired-pulse facilitation increase, respectively. This inhibition by AA was unaffected by cyclo- and lipo-oxygenase inhibitors, indomethacin (20 muM) and nordihydroguaiaretic acid (NDGA, 50 muM) or by the free radical scavenger, N-acetyl-L-Cysteine (0.5 mM). The K+ (20 mm)-evoked release of [H-3]glutamate from superfused hippocampal synaptosomes was inhibited by 18-39% by domoate (1-10 RM), an effect attenuated by 35-63% by AA (10 muM). Finally, the K-D (40-55 nM) of the kainate receptor agonist [H-3]-(2S,4R)-4-methylglutamate ([H-3]MGA) (0.3-120 nM) binding to hippocampal synaptosomal membranes was increased by 151-329% by AA (1-10 muM). These results indicate that AA directly inhibits presynaptic kainate receptor controlling glutamate release in the CA1 area of the rat hippocampus. (C) 2003 Elsevier Ltd. All rights reserved.