Received 2002-02-08 Accepted 2002-09-27
This work was supported by the National Natural Science Foundation of China (No.39770850)
*Corresponding author.
美加明和六烃季铵在交感神经元烟碱受体上作用位点的差异
刘卫, 郑建全*, 刘振伟, 李立君, 万勤, 刘传缋
军事医学科学院毒物药物研究所, 北京 100850
摘要: 为比较美加明和六烃季铵在交感神经元烟碱受体上作用位点的差异, 本文用膜片箝全细胞记录技术研究了美加明和六烃季铵对交感神经元烟碱诱发电流的抑制作用。在培养的颈上神经节细胞上, 美加明和六烃季铵拮抗烟碱作用的IC50分别为0.0012和0.0095 mmol/L, 并且都加速烟碱受体脱敏。在－30、 －70和 －110 mV钳制电压下, 美加明和六烃季铵抑制烟碱诱发电流的作用有电压依赖性。但是, 在每隔3 min连续给药的情况下, 美加明的作用有使用依赖性而六烃季铵没有。这表明美加明和六烃季铵在交感神经元烟碱受体上的作用位点不同。
关键词: 烟碱受体; 膜片箝; 交感神经元; 变构调节; 拮抗剂
学科分类号: Q425
Difference in action sites between mecamylamine and hexamethonium on nicotinic receptors of
sympathetic
neurons
Liu Wei, Zheng Jian-Quan, Liu Zhen-Wei, Li Li-Jun, Wan Qin, Liu Chuan-Gui
Institute
of Toxicology and Pharmacology,
Abstract: To compare the difference in action sites between mecamylamine and hexamethonium on nicotinic receptors of sympathetic neurons, We investigated the effects of mecamylamine and hexamethonium on the nicotine-induced currents in cultured superior cervical ganglion neurons by whole-cell patch clamp technique. The IC50 of mecamylamine and hexamethonium for antagonizing 0.08 mmol/L nicotine was 0.0012 and 0.0095 mmol/L, respectively. Both mecamylamine and hexamethonium accelerated the desensitization of nicotinic receptors. Furthermore, by comparing their effects at holding potential －30,－70 and －110 mV, it was indicated that their suppression effect on the nicotine-induced currents was voltage-dependent. However, different from that of hexamethonium, the inhibitory effect of mecamylamine increased with administrating the mixture of mecamylamine and nicotine at intervals of 3 min, indicating a use-dependent effect of mecamylamine. It is concluded that the action site of mecamylamine on nicotinic receptors of sympathetic neurons is different from that of hexamethonium.
Key words: nicotinic receptors; patch clamp technique; sympathetic neurons; allosteric modulation; antagonist