Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
Eur J Pharmacol. 2009 Oct 1;619(1-3):33-7. doi: 10.1016/j.ejphar.2009.08.011. Epub 2009 Aug 15.
In pharmacological studies using cultured neurones or heterologous expression systems, the N-methyl-d-aspartate (NMDA) receptor has been found as a major target for the inhalational anaesthetic xenon (Xe). NMDA receptors play a crucial role in behavioural and cellular processes related to learning and memory, and NMDA receptor subunits type 2A (NR2A) and type 2B (NR2B) are critical determinants for synaptic plasticity. In the present study, we investigated in an acute mouse brain slice preparation of the basolateral amygdala whether the antagonism of Xe is subunit-selective against the NR2A or NR2B subunit. From principal neurones, pharmacologically isolated NMDA receptor-mediated currents (p-NMDA-Cs) were evoked upon focal photolysis of caged L-glutamate and recorded using the whole-cell patch-clamp technique. To test whether the Xe-induced inhibition of NMDA receptor-mediated currents is selective for NR2A or NR2B subunits, p-NMDA-Cs were recorded in the presence of the NR2A or NR2B subunit antagonists R-S-1-4-bromophenylethylamino-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl-methylphosphonic acid (NVP-AAM077, 50 nM) or R-R*,S*-alpha-4-Hydroxyphenyl-beta-methyl-4-phenylmethyl-1-piperidinepropanol hydrochloride (Ro 25-6981, 0.5 microM), respectively. The Xe-induced reduction under these conditions was not significantly different from that without NR2A or NR2B blockade. These results provide evidence, that the Xe-induced antagonism against NMDA receptors is non-selective against NR2A- or NR2B-containing receptors.
在使用培养的神经元或异源表达系统进行药理学研究时，已发现 N-甲基-D-天冬氨酸（NMDA）受体是吸入麻醉剂氙（Xe）的主要靶标。 NMDA 受体在与学习和记忆有关的行为和细胞过程中起关键作用，并且 NMDA 受体亚基 2A（NR2A）和 2B（NR2B）是突触可塑性的关键决定因素。在本研究中，我们在急性小鼠大脑皮层切片中研究了外侧杏仁核的制备情况，以确定 Xe 对 NR2A 或 NR2B 亚基的拮抗作用是否具有亚基选择性。在使用全细胞膜片钳技术对药理学分离的 NMDA 受体介导的电流（p-NMDA-Cs）进行记录时，从主要神经元中通过笼锁 L-谷氨酸的焦点光解来诱发 NMDA 受体介导的电流。为了测试 Xe 诱导的 NMDA 受体介导的电流抑制是否对 NR2A 或 NR2B 亚基具有选择性，我们在存在 NR2A 或 NR2B 亚基拮抗剂 R-S-1-4-溴苯乙胺基-2,3-二氧代-1,2,3,4-四氢喹喔啉-5-基-甲基膦酸（NVP-AAM077，50 nM）或 R-R*，S*-α-4-羟基苯基-β-甲基-4-苯基甲基-1-哌啶丙烷醇盐酸盐（Ro 25-6981，0.5 μM）的情况下记录 p-NMDA-Cs。在没有 NR2A 或 NR2B 阻断的情况下，Xe 引起的减少没有显着差异。这些结果提供了证据，表明 Xe 诱导的 NMDA 受体拮抗作用对 NR2A 或 NR2B 包含的受体没有选择性。
