Taurine Targets the GluN2b-Containing NMDA Receptor Subtype
Taurine Targets the GluN2b-Containing NMDA Receptor Subtype
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DOI：
10.1007/978-3-319-15126-7_43
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发表时间：
2015-01-01
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影响因子：
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通讯作者：
Banerjee, Shailesh P.
中科院分区：
文献类型：
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作者：
Chan, Christopher Y.;Singh, Inderbir;Banerjee, Shailesh P.
作为中枢神经系统中的一种内源性神经调节剂，牛磺酸与TAG（6-氨甲基-3-甲基-4H-1，2，4-苯并噻二嗪1，1-二氧化物）敏感性和TAG不敏感性受体相互作用。牛磺酸通过打开Cl−通道激活前者，通过抑制谷氨酸NMDA受体激活后者。我们试图解决的网站牛磺酸的相互作用与NMDA受体。我们记录了内侧前额叶皮层切片的诱发场电位，并比较了Ro 25 -6981（GluN 1/GluN 2B NMDA受体亚型的选择性拮抗剂）在牛磺酸存在或不存在的情况下的剂量依赖性抑制。结果表明，牛磺酸对诱发反应的抑制作用与Ro 25 -6981的抑制作用重叠，提示牛磺酸通过作用于NMDA GluN 1/GluN 2B受体亚型来调节NMDA受体。[3 H]亚精胺和[3 H]牛磺酸与粗额皮质膜的特异性结合的置换表明，多胺和牛磺酸可能在一个共同的结合位点相互作用，可能位于GluN 1或GluN 2B亚基。我们还测试了长期牛磺酸对谷氨酸受体亚单位的作用，使用蛋白质印迹法测定慢性牛磺酸治疗后大鼠额叶皮质制备的突触体膜中NMDA和AMPA受体亚单位的表达。每天腹腔注射30次牛磺酸（100 mg/kg）可显著增加NMDA GluN 2B亚基的表达，但不增加GluN 1亚基的表达，并降低AMPA GluR 2亚基的表达。GluN 2B亚基的上调表明其与牛磺酸的长期相互作用，并支持其成为牛磺酸作用的主要靶点。AMPA GluR 2亚基的下调可能与GluR 2亚基缺乏的AMPA受体钙渗透亚型的募集增加相关。
As an endogenous neuromodulator in the CNS, Taurine interacts with TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide)-sensitive and TAG-insensitive receptors. Taurine activates the former by opening a Cl−channel and the latter by inhibiting the glutamate NMDA receptor. We sought to resolve the site of taurine’s interaction with the NMDA receptor. We recorded evoked field potential in medial prefrontal cortical slices and compared its dose-dependent inhibition by Ro25-6981, a selective antagonist for the GluN1/GluN2B NMDA receptor sub-type, in the absence or presence of taurine. The result revealed that inhibition of evoked responses mediated by taurine overlapped with that by Ro25-6981, suggesting that taurine modulates NMDA receptor by acting on the NMDA GluN1/GluN2B receptor sub-type. Displacement of specific binding of [3H]spermidine and of [3H]taurine to crude frontal cortical membranes by spermine and spermidine showed that polyamines and taurine may interact at a common binding site, possibly localized at the GluN1 or GluN2B subunit. We also tested for long-term taurine actions on glutamate receptor subunits using western blot determination of NMDA and AMPA receptor subunits expression in synaptosomal membranes prepared from rat frontal cortex following chronic taurine treatment. Thirty daily i.p. injections of taurine (100 mg/kg) significantly increased expression of the NMDA GluN2B, but not GluN1, subunit and decreased expression of the AMPA GluR2 subunit. The up-regulation of the GluN2B subunit suggests its long-term interaction with taurine, and supports its being a major target for taurine action. Down-regulation of the AMPA GluR2 subunit is possibly correlated to an increased recruitment of the GluR2-subunit-lacking, calcium-permeable subtype of AMPA receptor.