Xu Zucai, Xu Ping, Chen Yalan, Liu Jing, Zhang Yanke, Lv Yaodong, Luo Jing, Fang Min, Zhang Jun, Wang Jing, Wang Kewei, Wang Xuefeng, Chen Guojun
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China.
Neuromolecular Med. 2015 Mar;17(1):1-11. doi: 10.1007/s12017-014-8338-2. Epub 2014 Dec 10.
Type 1 equilibrative nucleoside transporter (ENT1) promotes glutamate release by inhibition of adenosine signaling. However, whether ENT1 plays a role in epileptic seizure that involves elevated glutamatergic neurotransmission is unknown. Here, we report that both seizure rats and patients show increased expression of ENT1. Intrahippocampal injection of a specific inhibitor of ENT1, nitrobenzylthioinosine (NBTI), attenuates seizure severity and prolongs onset latency. In order to examine whether NBTI would be effective as antiepileptic after peripheral application, we injected NBTI intraperitoneally, and the results were similar to those obtained after intrahippocampal injection. NBTI administration leads to suppressed neuronal firing in seizure rats. In addition, increased mEPSC in seizure are inhibited by NBTI. Finally, NBTI results in deactivation of phosphorylated cAMP-response element-binding protein in the seizure rats. These results indicate that ENT1 plays an important role in the development of seizure. Inhibition of ENT1 might provide a novel therapeutic approach toward the control of epileptic seizure.
1型平衡核苷转运体（ENT1）通过抑制腺苷信号促进谷氨酸释放。然而，ENT1是否在涉及谷氨酸能神经传递增强的癫痫发作中起作用尚不清楚。在此，我们报告癫痫大鼠和患者均显示ENT1表达增加。海马内注射ENT1特异性抑制剂硝基苄硫肌苷（NBTI）可减轻癫痫发作严重程度并延长发作潜伏期。为了研究外周应用NBTI是否作为抗癫痫药物有效，我们腹腔注射NBTI，结果与海马内注射后获得的结果相似。给予NBTI可抑制癫痫大鼠的神经元放电。此外，NBTI可抑制癫痫发作时增加的微小兴奋性突触后电流（mEPSC）。最后，NBTI导致癫痫大鼠中磷酸化的环磷酸腺苷反应元件结合蛋白失活。这些结果表明ENT1在癫痫发作的发展中起重要作用。抑制ENT1可能为控制癫痫发作提供一种新的治疗方法。
