Volatile anesthetics inhibit NMDA-stimulated 45Ca uptake by rat brain microvesicles.
Volatile anesthetics inhibit NMDA-stimulated 45Ca uptake by rat brain microvesicles.
复制标题
挥发性麻醉剂抑制 NMDA 刺激的大鼠脑微泡对 45Ca 的吸收。
DOI：
10.1007/bf00968999
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发表时间：
1994
影响因子：
4.4
通讯作者：
Dennison,RL
中科院分区：
文献类型：
--
作者：
Aronstam,RS;Martin,DC;Dennison,RL
我们之前已经证明，挥发性麻醉剂会抑制谷氨酸刺激的 [3H]MK-801 与大鼠脑中 NMDA 受体复合物离子载体的结合。在本研究中，我们研究了安氟烷和氟烷对从大鼠脑中分离的微泡组分吸收 NMDA 刺激的 45Ca 的影响。 NMDA 刺激大鼠脑微泡吸收 45Ca（30 秒）高达 70%，EC50 为 1.4±0.5 μM。 NMDA 刺激的 45Ca 摄取被 MK-801 和 D-AP-5 抑制，IC50 约为 10 μM。安氟烷和氟烷抑制 100 μM NMDA 刺激的 45Ca 摄取高达 60-80%，IC50 为 0.2-0.3 mM，在常规临床使用中达到的浓度。在没有激动剂的情况下测量的Basal45Ca摄取不受麻醉剂的影响。甘氨酸不影响NMDA刺激的45Ca摄取水平，但显着降低安氟烷和氟烷引起的摄取抑制。微泡与 NMDA 预孵育导致 NMDA 刺激的 45 Ca 摄取脱敏，t1/2 约为 20 秒。安氟烷和氟烷降低了这种脱敏的程度和发展速度，甘氨酸也是如此。这些发现支持这样的观点：挥发性麻醉剂对 NMDA 受体复合物神经传递的干扰有助于麻醉状态的发展。
We have previously shown that volatile anesthetics inhibit glutamate-stimulated [3H]MK-801 binding to the ionophore of NMDA receptor complexes in rat brain. In the present study, we examined the influence of enflurane and halothane on NMDA-stimulated45Ca uptake by a microvesicle fraction isolated from rat brain. NMDA stimulated45Ca uptake (30 sec) by rat brain microvesicles by up to 70% with an EC50of 1.4±0.5 μM. The NMDA-stimulated45Ca uptake was inhibited by MK-801 and D-AP-5 with IC50's of ≈10 μM. Enflurane and halothane inhibited45Ca uptake stimulated by 100 μM NMDA by as much as 60–80% with IC50's of 0.2–0.3 mM, concentrations achieved during routine clinical use. Basal45Ca uptake measured in the absence of agonist was not affected by the anesthetics. Glycine did not affect the level of NMDA-stimulated45Ca uptake, but markedly reduced the inhibition of uptake caused by enflurane and halothane. Preincubation of microvesicles with NMDA resulted in a desensitization of NMDA-stimulated45Ca uptake, with a t1/2of ≈20 sec. Enflurane and halothane diminished both the extent and rate of development of this desensitization, as did glycine. These findings support the idea that volatile anesthetic interference with neurotransmission at NMDA receptor complexes contributes to the development of the anesthetic state.