挥发性麻醉药和n -甲基- d -谷氨酸激活受体。
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马丁,Plagenhoef M,亚伯拉罕J,老板RL Aronstam RS
挥发性麻醉药和n -甲基- d -谷氨酸激活受体。
生物化学杂志。1995年3月15日,49(6):809 - 17所示。
- PubMed ID
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7702639 (在PubMed]
- 文摘
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几项研究已经显示重要的功能之间的交互挥发性麻醉剂和n -甲基- d (NMDA)类的谷氨酸受体。在目前的研究中,我们审查的影响乙醚,氯仿,甲氧氟烷,氟烷、安氟醚、异氟烷和在(1)谷氨酸NMDA受体的激活复杂,包括甘氨酸逆转的麻醉作用,所透露的[3 h] - (5 r, 10 s) - (+) methyl-10 11-dihydro-5H-dibenzo [a, d] cyclohepten-5 10-imine, dizocilpine (mk - 801)绑定到阳离子通道,和(2)[3 h] cis-4——(phosphonomethyl) piperidine-2-carboxylic酸19755 (CGS)绑定到谷氨酸NMDA受体的识别网站与之前的研究结果相一致,谷氨酸的绑定增加1 nM [3 h] mk - 801, 1小时后测量孵化在37度,达数百倍。这种刺激,被谷氨酸拮抗剂,会使甘氨酸的EC50大约0.03妈妈。甘氨酸也有直接刺激作用[3 h] mk - 801绑定在更高浓度(> = 10妈妈)。所有的麻醉剂检查抑郁谷氨酸刺激[3 h] mk - 801浓度的方式绑定以下效力顺序:氟烷>或=安氟醚>甲氧氟烷>氯仿>乙醚。这种抑制[3 h] mk - 801绑定被观察到在脑脊液浓度通常达到外科麻醉。此外,抑制被推翻后迅速去除麻醉剂的试验介质。加入甘氨酸在孵化中明显减毒anesthetic-induced抑制glutamate-sensitive [3 h] mk - 801绑定的EC50 0.1和1之间的妈妈。因此,这种逆转由甘氨酸与增效而不是其直接的刺激,对NMDA受体的影响。麻醉抑制[3 h] mk - 801绑定不能克服通过提高谷氨酸浓度(即交互似乎并未竞争对谷氨酸)除非甘氨酸。 Binding of [3H]CGS 19755 to the glutamate recognition site was also inhibited by each of the anesthetics examined. However, with the exception of chloroform, all of the anesthetics were more potent inhibitors of glutamate-stimulated [3H]MK-801 binding than they were of [3H]CGS 19755 binding. [3H]CGS 19755 binding saturation curves in the presence of halothane and enflurane indicated a decrease in the density of [3H]-CGS 19755 binding sites with no change in binding affinity (i.e. the inhibition did not appear to be competitive). These findings support the idea that anesthetic drugs disrupt NMDA receptor transmission through multiple allosteric effects on the receptor-channel activation mechanisms and the glutamate binding site.