Omerovic A, Leonard J P, Kelso S R
Department of Biological Sciences, University of Illinois at Chicago 60680.
Brain Res Mol Brain Res. 1994 Mar;22(1-4):89-96. doi: 10.1016/0169-328x(94)90035-3.
We have examined the effects of oxidizing and reducing agents and sodium nitroprusside (SNP) on currents evoked by NMDA (N-methyl-D-aspartate) using the Xenopus oocyte expression system. Oocytes were injected with RNA prepared from either whole rat brain or from the NMDAR1 clone recently isolated from rat brain. Bath application of 1-1000 microM SNP, which releases nitric oxide and ferrocyanide, caused a rapid inhibition of NMDA-evoked current in both preparations. The inhibitory effect reversed spontaneously within 15 min. Kainate responses were not affected by SNP. Exposure to the reducing agent, dithiothreitol (DTT), enhanced NMDA currents; the oxidant, 5,5-dithio-bis-2-nitrobenzoic acid (DTNB), inhibited NMDA responses, as has been observed in other preparations. The site of action of SNP appeared to be different than the DTT/DTNB redox site for several reasons: SNP and DTNB inhibitions were additive at high doses, DTT did not rapidly reverse SNP effects, and SNP and DTT treatments did not show the same susceptibility to block by the NMDA antagonist, aminophosphonovaleric acid (APV). The results demonstrate that modulation of NMDA receptors by SNP is a property of homomeric channels and is retained when the NMDAR1 subunit is expressed in oocytes.
我们使用非洲爪蟾卵母细胞表达系统，研究了氧化还原剂和硝普钠（SNP）对N-甲基-D-天冬氨酸（NMDA）诱发电流的影响。向卵母细胞注射从大鼠全脑或最近从大鼠脑分离出的NMDAR1克隆制备的RNA。向浴槽中加入1-1000微摩尔的SNP（可释放一氧化氮和亚铁氰化物），可迅速抑制两种制剂中NMDA诱发的电流。这种抑制作用在15分钟内自发逆转。海人酸反应不受SNP影响。如在其他制剂中所观察到的，暴露于还原剂二硫苏糖醇（DTT）可增强NMDA电流；氧化剂5,5'-二硫代双（2-硝基苯甲酸）（DTNB）可抑制NMDA反应。SNP的作用位点似乎与DTT/DTNB氧化还原位点不同，原因如下：高剂量时SNP和DTNB的抑制作用具有加和性，DTT不能迅速逆转SNP的作用，并且SNP和DTT处理对NMDA拮抗剂氨基磷酸戊酸（APV）阻断的敏感性不同。结果表明，SNP对NMDA受体的调节是同源通道的一种特性，并且当NMDAR1亚基在卵母细胞中表达时该特性仍然保留。
