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

Difference in action sites between mecamylamine and hexamethonium on nicotinic receptors of sympathetic neurons

为比较美加明 (mecamylamine,MEC)和六烃季铵 (hexamethonium ,HEX)在交感神经元烟碱受体上作用位点的差异 ,实验用膜片钳全细胞记录技术研究了MEC和HEX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 ,MEC和HEX拮抗烟碱作用的IC50 分别为 0 0 0 12和 0 0 0 95mmol/L ,并且都加速烟碱受体脱敏。在 - 3 0、 - 70和 - 110mV钳制电压下 ,MEC和HEX抑制烟碱诱发电流的作用有电压依赖性。但在每隔 3min连续给药的情况下 ,MEC的作用有使用依赖性而HEX没有 。

To compare the difference in action sites between mecamylamine (MEC) and hexamethonium (HEX) on nicotinic receptors of sympathetic neurons, we investigated the effects of MEC and HEX on the nicotine-induced currents in cultured superior cervical ganglion neurons by whole-cell patch clamp technique. The IC 50 of MEC and HEX for antagonizing the effect of 0.08 mmol/L nicotine was 0.0012 and 0.0095 mmol/L, respectively. Both MEC and HEX accelerated the desensitization of nicotinic receptors. Furthermore, by comparing their effects at holding potentials -30, -70 and -110 mV, it was indicated that their suppressing effect on the nicotine-induced currents was voltage-dependent. However, different from that of HEX, the inhibitory effect of MEC increased with administrating the mixture of MEC and nicotine at intervals of 3 min, indicating a use-dependent effect of MEC. It is concluded that the action site of MEC on nicotinic receptors of sympathetic neurons is different from that of HEX.