Sung J J, Kim S J, Lee H B, Chung J M, Choi Y M, Cha C I, Suh Y H, Lee K W
Department of Pharmacology, Neuroscience Research Institute, Seoul, Korea.
Muscle Nerve. 1998 Sep;21(9):1135-44. doi: 10.1002/(sici)1097-4598(199809)21:9<1135::aid-mus4>3.0.co;2-8.
The effects of carbamate anticholinesterases, pyridostigmine and physostigmine, on the function of the nicotinic receptor (nAChR) in TE671 cells was studied, precluding their inhibition of acetylcholine hydrolysis by carbachol usage. In radioassay, the simultaneous application of carbachol and carbamates dose-dependently decreased carbachol-induced 22Na+ influx, compared with carbachol activation alone. Increasing cell preincubation in the presence of carbamates, however, potentiated influx at low concentrations in a time-dependent manner. This facilitating effect of carbamates, even at high concentrations, was significantly increased by washing out these drugs and was blocked by pretreatment with diisopropylfluorophosphate. Similar results were also obtained in whole-cell patch-clamp study. There were insignificant changes in desensitization properties during facilitation. It is thus supposed that facilitation cannot be explained by the inhibition of acetylcholine hydrolysis. These results support a previous hypothesis that acetylcholinesterase might modulate nAChR by an unknown mechanism. In addition, the clinical effects of carbamates may be partly attributed to this facilitation.
研究了氨基甲酸酯类抗胆碱酯酶药吡啶斯的明和毒扁豆碱对TE671细胞烟碱样受体（nAChR）功能的影响，通过使用卡巴胆碱排除了它们对乙酰胆碱水解的抑制作用。在放射分析中，与单独使用卡巴胆碱激活相比，同时应用卡巴胆碱和氨基甲酸酯类药物可剂量依赖性地降低卡巴胆碱诱导的22Na+内流。然而，在氨基甲酸酯类药物存在的情况下增加细胞预孵育时间，可使低浓度时的内流呈时间依赖性增强。即使在高浓度下，氨基甲酸酯类药物的这种促进作用在洗去这些药物后也显著增强，并被二异丙基氟磷酸预处理所阻断。在全细胞膜片钳研究中也得到了类似的结果。在促进过程中，脱敏特性没有明显变化。因此推测，促进作用不能用抑制乙酰胆碱水解来解释。这些结果支持了先前的一个假设，即乙酰胆碱酯酶可能通过一种未知机制调节nAChR。此外，氨基甲酸酯类药物的临床效果可能部分归因于这种促进作用。
