Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
Pharmacol Rep. 2013;65(3):650-7. doi: 10.1016/s1734-1140(13)71042-9.
Glutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We investigated the effect of agents modulating the activity of these systems on the experimental ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled nitric oxide (eNO) levels.
We used the agonists of NMDA receptors - N-methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective competitive antagonist (DL-2-amino-5-phosphonovaleric acid - AP-5) and selective non-competitive antagonist (dizocilpine - MK-801) of these receptors. We used also non-specific inhibitor of NO synthases N(ω)-nitro-L-arginine methyl ester (L-NAME). The airways responsiveness to histamine or acetylcholine was evaluated under in vitro conditions.
NMDA administration caused the increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5 provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth muscle. We recorded the changes in eNO levels. The activation of NMDA receptor with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME caused the fall of eNO levels. MK-801 shows (within the group) the more expressive effect in the eNO levels during sensitization than AP-5 group.
The results confirm the possibility of NMDA receptors participation in the experimental airways hyperreactivity.
谷氨酸能和硝能系统参与呼吸系统功能的控制。关于这两个系统在气道高反应性中的相互作用，信息很少。我们研究了调节这些系统活性的药物对实验性卵白蛋白诱导的气道高反应性以及呼气一氧化氮（eNO）水平变化的影响。
我们使用 NMDA 受体激动剂 - N-甲基-D-天冬氨酸（NMDA）和单谷氨酸钠（MSG）、这些受体的选择性竞争性拮抗剂（DL-2-氨基-5-磷戊酸 - AP-5）和选择性非竞争性拮抗剂（地卓西平 - MK-801）。我们还使用非特异性一氧化氮合酶抑制剂 N（ω）-硝基-L-精氨酸甲酯（L-NAME）。在体外条件下评估了气道对组胺或乙酰胆碱的反应性。
NMDA 给药导致卵白蛋白诱导的乙酰胆碱高反应性中气管平滑肌反应增加。MSG 的作用不那么明显。MK-801 和 AP-5 主要引起气管平滑肌对乙酰胆碱反应性下降。我们记录了 eNO 水平的变化。NMDA 或 MSG 激活 NMDA 受体增加了 eNO 水平。用 L-NAME 抑制一氧化氮合酶导致 eNO 水平下降。MK-801 在致敏期间显示出比 AP-5 组更明显的 eNO 水平效应（组内）。
结果证实 NMDA 受体参与实验性气道高反应性的可能性。
