神经元N受体α4β2亚型在激动剂作用下功能失敏后再激活及宾赛克嗪的拮抗作用

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (10): 1091-1094.

神经元N受体α4β2亚型在激动剂作用下功能失敏后再激活及宾赛克嗪的拮抗作用

罗王倩¹, 崔文玉¹, 汪海^1,2

¹军事医学科学院毒物药物研究所, 北京 100850;
²军事医学科学院卫生学环境医学研究所, 天津 300050

收稿日期:2008-04-14 修回日期:2008-09-23 出版日期:2008-10-26 发布日期:2020-10-19
通讯作者: 汪海,男,博士,研究员,博士生导师,研究方向:分子药理学和心脑血管创新药物研究。Tel:010-66932651 　E-mail:wh9588@yahoo.com.cn
作者简介:罗王倩,男,博士研究生, 研究方向:神经药理及神经电生理。Tel:010-66874608 　 E-mail:luowangqian2004@163.com
基金资助:
国家自然科学基金项目(30371641)

Reactivation of neuronal α4β2-nicotinic acetylcholine receptors following desensitization induced by agonist was blocked by benthiactzine

LUO Wang-qian¹, CUI Wen-yu¹, WANG Hai^1,2

¹Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences, Beijing 100850, China;
²Institute of Hygiene and Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China

Received:2008-04-14 Revised:2008-09-23 Online:2008-10-26 Published:2020-10-19

摘要/Abstract

摘要： 目的: 研究神经元N受体α4β2亚型在激动剂持续作用下,功能失敏后再激活,以及宾赛克嗪的拮抗作用。方法: 在转染后稳定表达神经元N受体α4β2亚型的SH-EP1细胞株上,以烟碱为工具药,通过喷射给药,采用膜片钳全细胞记录技术进行研究。结果: 快速给予1mmol/L浓度的烟碱,可诱发一内向电流,该电流快速激活达到峰值后,在激动剂持续作用下迅速失敏至基线附近。当激动剂去除后可再次记录到一内向电流,该电流可被新型胆碱受体拮抗剂宾赛克嗪所阻断。结论: SH-EP1细胞株转染表达的神经元N受体α4β2亚型在高浓度激动剂持续作用下发生功能失敏,当激动剂去除后可再度激活,此再激活过程可被新型胆碱受体拮抗剂宾赛克嗪所拮抗。

关键词: N受体, 有机磷中毒, 反跳, 宾赛克嗪, 膜片钳

Abstract: AIM: To investigate the reactivation of neuronal α4β2-nicotinic acetylcholine receptors following desensitization induced by agonist and the antagonism of benthiactzine against it .METHODS: The whole cell recording configuration of patch-clamp technique and the rapid application of nicotine were performed in α4β2-nAChRs heterologously expressed in cultured SH-EP1 cells. RESULTS: An inward current was elicited by rapid application of 1 mmol/L nicotine in SH-EP1 cells.This current reached peak rapidly and then desensitized fast when the application of agonist was prolonged. However, after the removal of nic-otine, an additional inward current reoccurred. This rebound current can be blocked by benthiactzine, a new antagonist of cholinergic receptors. CONCLUSION: Neuronal α4β2-nicotinic acetylcholine receptor heterologously expressed in the SH-EP1 cell line can be desensitized by prolonged agonist application, and be reactivated after the removal of agonist .This reactivat-ed current can be blocked by benthiactzine, a new an- tagonist of cholinergic receptors.

Key words: nicotinic acetylcholine receptors, or-ganophosphate poisoning, rebound, benthiactzine, patch clamp

中图分类号:

R965.2

罗王倩, 崔文玉, 汪海. 神经元N受体α4β2亚型在激动剂作用下功能失敏后再激活及宾赛克嗪的拮抗作用[J]. 中国临床药理学与治疗学, 2008, 13(10): 1091-1094.

LUO Wang-qian, CUI Wen-yu, WANG Hai. Reactivation of neuronal α4β2-nicotinic acetylcholine receptors following desensitization induced by agonist was blocked by benthiactzine[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(10): 1091-1094.

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