Increased brain monoaminergic tone after the NMDA receptor GluN2A subunit gene knockout is responsible for resistance to the hypnotic effect of nitrous oxide.
Increased brain monoaminergic tone after the NMDA receptor GluN2A subunit gene knockout is responsible for resistance to the hypnotic effect of nitrous oxide.
复制标题
NMDA 受体 GluN2A 亚基基因敲除后，大脑单胺能张力增加，是抵抗一氧化二氮催眠作用的原因。
DOI：
10.1016/j.ejphar.2012.10.034
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发表时间：
2013
影响因子：
5
通讯作者：
H. Baba
中科院分区：
文献类型：
--
作者：
A. Petrenko;T. Yamakura;T. Kohno;K. Sakimura;H. Baba
N-甲基-d-天冬氨酸 (NMDA) 受体可以在体外被临床相关浓度的吸入麻醉剂抑制。在这里，为了阐明 NMDA 受体在麻醉引起的意识丧失中的作用，我们检查了异氟烷、七氟烷和一氧化二氮对 NMDA 受体 GluN2A 亚基敲除小鼠的催眠特性。通过测量 LORR 的 50% 浓度 (LORR ED50)，在小鼠翻正反射丧失 (LORR) 试验中评估吸入麻醉药的催眠特性。基因敲除小鼠表现出与野生型对照相似的异氟烷和七氟烷 LORR ED50 值，表明这些受体对卤化麻醉剂的催眠作用没有显着贡献。然而，与野生型对照相比，突变小鼠在一氧化二氮存在下表现出更大的异氟烷 LORR ED50 值，表明对这种气体麻醉剂的抵抗力。基因敲除小鼠的脑单胺能活性增强，这是继发于 NMDA 受体功能障碍的，并且观察到的对一氧化二氮的异氟烷 LORR ED50 保留作用的抵抗性可以通过用多巴胺 D2 受体拮抗剂氟哌利多或血清素 5-HT2A 受体拮抗剂酮色林预处理来消除。因此，基因敲除小鼠对一氧化二氮的抵抗似乎是单胺能起源的继发现象，而不是 NMDA 受体功能受损的直接结果。我们的研究结果表明，NMDA 受体与常规吸入麻醉剂的催眠作用无关。此外，他们还认为，增加大脑单胺能张力可以减弱全身麻醉的效果。最后，他们提供了进一步的证据，证明基因操作继发的变化可以解释全球基因敲除中获得的结果。
N-methyl-d-aspartate (NMDA) receptors can be inhibited by inhalational anesthetics in vitro at clinically relevant concentrations. Here, to clarify the role of NMDA receptors in anesthetic-induced unconsciousness, we examined the hypnotic properties of isoflurane, sevoflurane and nitrous oxide in NMDA receptor GluN2A subunit knockout mice. The hypnotic properties of inhalational anesthetics were evaluated in mice in the loss of righting reflex (LORR) assay by measuring the 50% concentration for LORR (LORR ED50). Knockout mice displayed isoflurane and sevoflurane LORR ED50values similar to wild-type controls, indicating no significant contribution of these receptors to the hypnotic action of halogenated anesthetics. However, compared with wild-type controls, mutant mice displayed larger isoflurane LORR ED50values in the presence of nitrous oxide, indicating a resistance to this gaseous anesthetic. Knockout mice have enhanced brain monoaminergic activity which occurs secondary to NMDA receptor dysfunction, and the observed resistance to the isoflurane LORR ED50-sparing effect of nitrous oxide could be abolished by pretreatment with the dopamine D2receptor antagonist droperidol or with the serotonin 5-HT2Areceptor antagonist ketanserin. Thus, resistance to nitrous oxide in knockout mice appears to be a secondary phenomenon of monoaminergic origin and not a direct result of impaired NMDA receptor function. Our results indicate that NMDA receptors are not critically involved in the hypnotic action of conventionally-used inhalational anesthetics. Also, they suggest that increased brain monoaminergic tone can diminish the effects of general anesthesia. Finally, they provide further evidence that changes secondary to genetic manipulation can explain the results obtained in global knockouts.
甲基苯丙胺对戊巴比妥麻醉大鼠的兴奋作用是通过多巴胺能胆碱能机制介导的。
DOI：
--
发表时间：
1994
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Horita,A;Carino,MA;Ukai,Y
通讯作者：
Ukai,Y
影响因子：
2.8
作者：
Watson, Christopher J;Baghdoyan, Helen A;Lydic, Ralph
通讯作者：
Lydic, Ralph