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|Title:||Presynaptic kainate receptors modulating glutamatergic transmission in the rat hippocampus are inhibited by arachidonic acid||Authors:||Cunha, Rodrigo A.
Ribeiro, J. A.
Malva, João O.
|Keywords:||Kainate; Arachidonic acid; Hippocampus; Synaptic transmission; Nerve terminals; Glutamate release; Binding||Issue Date:||2004||Citation:||Neurochemistry International. 44:5 (2004) 371-379||Abstract:||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 [mu]M) 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 [mu]M) 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 [mu]M) and nordihydroguaiaretic acid (NDGA, 50 [mu]M) or by the free radical scavenger, N-acetyl--cysteine (0.5 mM). The K+ (20 mM)-evoked release of [3H]glutamate from superfused hippocampal synaptosomes was inhibited by 18-39% by domoate (1-10 [mu]M), an effect attenuated by 35-63% by AA (10 [mu]M). Finally, the KD (40-55 nM) of the kainate receptor agonist [3H]-(2S,4R)-4-methylglutamate ([3H]MGA) (0.3-120 nM) binding to hippocampal synaptosomal membranes was increased by 151-329% by AA (1-10 [mu]M). These results indicate that AA directly inhibits presynaptic kainate receptor controlling glutamate release in the CA1 area of the rat hippocampus.||URI:||http://hdl.handle.net/10316/4790||Rights:||openAccess|
|Appears in Collections:||FMUC Medicina - Artigos em Revistas Internacionais|
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