Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine.
Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine.
复制标题
挥发性麻醉剂和 NMDA 受体。
DOI：
10.1016/0304-3940(91)90436-w
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发表时间：
1991
影响因子：
2.5
通讯作者：
Aronstam,RS
中科院分区：
文献类型：
--
作者：
Martin,DC;Abraham,JE;Plagenhoef,M;Aronstam,RS
在大鼠大脑皮质膜中测定了挥发性全身麻醉剂安氟醚对[3 H] MK-801与n -甲基-d-天门氨酸（NMDA）受体离子通道中一个位点结合的影响。安氟醚破坏了[3 H] MK-801 （1 nM）结合的谷氨酸刺激，ic50为0.4 mM。这种抑制与受体亲和力降低有关，但[3 H] MK-801结合位点的数量没有变化。在没有谷氨酸的情况下，基础[3 H] MK-801结合不受安氟醚的影响。相比之下，[3 H] CGS-19775与NMDA受体上谷氨酸识别位点的结合仅被安氟醚微弱抑制（例如，1.2 mM安氟醚对5 nM [3 H] CGS结合的抑制小于20%）。甘氨酸是一种正变构NMDA受体调节剂，能显著减弱氨氟醚对谷氨酸刺激的[3 H] MK-801结合的抑制作用，其EC 50约为0.8 μM。因此，安氟醚选择性地抑制NMDA受体的谷氨酸激活，而变构调节剂减弱了这一作用。这些效应可能反映了甘氨酸结合位点或影响离子通道激活的另一个未定义位点的麻醉作用。这些发现提出了抑制NMDA受体传递有助于麻醉状态发展的可能性。
The influence of enflurane, a volatile general anesthetic, on [3 H] MK-801 binding to a site in the ion channel of the N-methyl-d-aspartate (NMDA) receptor was determined in membranes from rat cerebral cortex. Enflurane disrupted glutamate stimulation of [3 H] MK-801 (1 nM) binding with an IC 50 of 0.4 mM. This inhibition was associated with a decrease in receptor affinity with no change in the number of [3 H] MK-801 binding sites. Basal [3 H] MK-801 binding measured in the absence of glutamate was not affected by enflurane. In contrast,[3 H] CGS-19775 binding to the glutamate recognition site on the NMDA receptor was only weakly inhibited by enflurane (eg, less than 20% inhibition of 5 nM [3 H] CGS binding by 1.2 mM enflurane). Glycine, a positive allosteric NMDA receptor modulator, markedly attenuated the inhibition of glutamate-stimulated [3 H] MK-801 binding by enflurane, with an EC 50 of approximately 0.8 μM. Thus, enflurane selectively inhibits glutamate activation of the NMDA receptors, and an allosteric modulator attenuates this action. These effects could reflect anesthetic action at the glycine binding site or at another, undefined site which influences activation of the ion channel. These findings raise the possibility that inhibition of transmission at NMDA receptors contributes to the development of the anesthetic state.