Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism.
Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism.
复制标题
花生四烯酸代谢抑制剂调节海马 CA1 区切片的谷氨酸和天冬氨酸释放。
DOI：
10.1046/j.1471-4159.1995.64031152.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
Nadler,JV
中科院分区：
文献类型：
--
作者：
Peterson,CL;Thompson,MA;Martin,D;Nadler,JV
用海马区CA1区的脑片检测花生四烯酸代谢抑制剂对CA3来源的Schaffer侧支、连合和同侧联合终末谷氨酸/天冬氨酸释放的影响。试验化合物[3微米二氢愈创木酸和1µM3‐[3‐(4‐chlorobenzyl)‐3‐tert‐butylthio‐5‐isopropylindol‐2‐yl]‐2，2‐dimethyl‐propanoic酸(MK-886)]可以减少5-脂氧合酶代谢产物的产生和释放，也选择性地减少K+引起的天冬氨酸的释放。相反，环氧合酶抑制剂吲哚美辛(100µM)选择性地促进谷氨酸的释放。在非选择性抑制花生四烯酸及其代谢物释放的浓度(100µM)下，NDGA显著抑制天冬氨酸、谷氨酸和GABA的释放。12-脂氧合酶抑制剂和一氧化氮合酶抑制剂不影响K+引起的任何递质氨基酸的释放。这些结果表明，5-脂氧合酶产物选择性地促进天冬氨酸的释放，而环氧合酶产物选择性地抑制谷氨酸的释放。它们也与先前的证据一致，即花生四烯酸和/或血小板激活因子促进谷氨酸和天冬氨酸的释放并抑制谷氨酸和天冬氨酸的摄取。与GABA的释放相比，K+引起的兴奋性氨基酸的释放对脂质介质的调节更为敏感。NMDA受体的激活可能通过刺激脂质调节剂的产生和释放，促进K+诱导的CA1脑片谷氨酸和天冬氨酸的释放。
Slices of hippocampal area CA1 were used to test inhibitors of arachidonic acid metabolism for their effects on glutamate/aspartate release from the CA3‐derived Schaffer collateral, commissural, and ipsilateral associational terminals. Test compounds [3 µMnordihydroguaiaretic acid (NDGA) and 1 µM3‐[3‐(4‐chlorobenzyl)‐3‐tert‐butylthio‐5‐isopropylindol‐2‐yl]‐2,2‐dimethyl‐propanoic acid (MK‐886)] that reduced the production and release of 5‐lipoxygenase metabolites also selectively reduced the K+‐evoked release of aspartate. In contrast, the cyclooxygenase inhibitor indomethacin (100 µM) selectively enhanced the release of glutamate. At a concentration (100 µM) that nonselectively depressed the release of arachidonic acid and its metabolites, NDGA markedly depressed the release of aspartate, glutamate, and GABA. An inhibitor of the 12‐lipoxygenase and an inhibitor of nitric oxide synthase did not affect the K+‐evoked release of any transmitter amino acid. These results suggest that a 5‐lipoxygenase product selectively enhances aspartate release and a cyclooxygenase product selectively depresses glutamate release. They are also consistent with previous evidence that arachidonic acid and/or platelet‐activating factor enhances the release and depresses the uptake of glutamate and aspartate. The K+‐evoked release of excitatory amino acids is much more sensitive to modulation by lipid mediators than is GABA release. Activation of NMDA receptors may enhance the K+‐evoked release of glutamate and aspartate from CA1 slices by stimulating the production and release of lipid modulators.