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 microM) 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 microM) 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 microM) and nordihydroguaiaretic acid (NDGA, 50 microM) or by the free radical scavenger, N-acetyl-L-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 microM), an effect attenuated by 35-63% by AA (10 microM). 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 microM). These results indicate that AA directly inhibits presynaptic kainate receptor controlling glutamate release in the CA1 area of the rat hippocampus.
Cunha
Rodrigo A
RA
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal. racunha@clix.pt
Ribeiro
J A
JA
Malva
João O
JO
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D016718:Arachidonic Acid; D016861:Cyclooxygenase Inhibitors; D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D018698:Glutamic Acid; D016859:Lipoxygenase Inhibitors; D009467:Neuromuscular Depolarizing Agents; D018092:Kainic Acid Receptors; D017661:Receptors, Presynaptic