Cunha Rodrigo A, Ribeiro J A, Malva João O
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
Neurochem Int. 2004 Apr;44(5):371-9. doi: 10.1016/s0197-0186(03)00167-0.
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.
海人酸受体是位于突触后膜的离子型谷氨酸受体，介导频率依赖性传递，也存在于突触前膜，调节递质释放。与兴奋性突触后海人酸受体不同，突触前海人酸受体也可以是抑制性的，其作用可能涉及代谢型作用。花生四烯酸（AA）可调节大多数离子型受体，特别是突触后海人酸受体介导的电流。为了进一步探究突触前海人酸受体和突触后海人酸受体之间的差异，我们测试了突触前海人酸受体是否受AA影响。海人酸（0.3 - 3微摩尔）和海人酸受体激动剂软骨藻酸（60 - 300纳摩尔）可使大鼠海马CA1区的场兴奋性突触后电位（fEPSP）斜率抑制19% - 54%，并使双脉冲易化（PPF）增加12% - 32%。AA（10微摩尔）分别使软骨藻酸（60 - 300纳摩尔）诱导的fEPSP抑制和双脉冲易化增加衰减37% - 72%和62% - 66%。AA的这种抑制作用不受环氧化酶和脂氧化酶抑制剂吲哚美辛（20微摩尔）和去甲二氢愈创木酸（NDGA，50微摩尔）或自由基清除剂N - 乙酰 - L - 半胱氨酸（0.5毫摩尔）的影响。软骨藻酸（1 - 10微摩尔）可使从灌流海马突触体中K⁺（20毫摩尔）诱发的[³H]谷氨酸释放抑制18% - 39%，AA（10微摩尔）可使这种作用衰减35% - 63%。最后，AA（1 - 10微摩尔）可使海人酸受体激动剂[³H] - (2S,4R) - 4 - 甲基谷氨酸（[³H]MGA）（0.3 - 120纳摩尔）与海马突触体膜结合的解离常数（KD）增加151% - 329%。这些结果表明，AA直接抑制大鼠海马CA1区控制谷氨酸释放的突触前海人酸受体。
