Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D,10S)-(+)-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain.
Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D,10S)-(+)-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain.
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DOI：
10.1016/0006-2952(95)02017-9
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发表时间：
1995-10
影响因子：
5.8
通讯作者：
D. Martin;R. Aronstam
中科院分区：
文献类型：
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作者：
D. Martin;R. Aronstam
在大鼠脑中研究了亚精胺（一种多胺激动剂）对挥发性麻醉剂抑制N-甲基-D-天冬氨酸（NMDA）受体活化的影响，如谷氨酸刺激[3 H]MK-801（[3 H]（5 D，10 S）-（+）-甲基-10，11-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺）结合所示。亚精胺保留了四种挥发性麻醉剂（安氟醚、氟烷、甲氧氟醚和氯仿）在相同浓度（EC 50 ~ 3 μM）下引起的抑制作用，在此浓度下，亚精胺增强了谷氨酸对NMDA离子通道的开放。麻醉剂对亚精胺直接刺激通道开放没有影响，在不存在受体激动剂的情况下，亚精胺浓度大于30 μM时发生。在这些作用中，亚精胺与别构共激动剂甘氨酸非常相似。目前的结果表明，麻醉剂对NMDA受体的作用涉及一组网站上的通道复合物，是不同的谷氨酸，甘氨酸和通道阻滞剂的识别位点，并与NMDA受体的封锁有助于麻醉状态的发展的想法是一致的。
The influence of spermidine, a polyamine agonist, on volatile anesthetic inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by glutamate stimulation of [3H]MK-801 ([3H](5 D ,10S)-(+)- methyl -10,11- dihydro -5H- dibenzo [a,d] cyclohepten -5,10- imine ) binding, was studied in rat brain. Spermidine reserved the inhibition caused by four volatile anesthetics (enflurane, halothane, methoxyflurane and chloroform) at the same concentrations (EC50≈ 3 μM) at which it potentiated glutamate opening of the NMDA ion channel. The anesthetics had no effect on the direct stimulation of channel opening by spermidine, which occurred at concentrations of spermidine greater than 30 μM in the absence of receptor agonist. In these actions, spermidine closely resembled the allosteric co-agonist glycine. The present results suggest that anesthetic action on NMDA receptors involves a set of sites on the channel complex that is distinct from the recognition sites for glutamate, glycine, and channel blockers, and are consistent with the idea that blockade of NMDA receptors contributes to the development of the anesthetic state.