Adler M, Moore D H, Filbert M G
Neurotoxicology Branch, Pathophysiology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010.
Arch Toxicol. 1992;66(3):204-10. doi: 10.1007/BF01974016.
The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine tracheal smooth muscle in vitro. Concentrations of soman greater than or equal to 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman greater than or equal to 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction.
在体外对犬气管平滑肌研究了不可逆有机磷胆碱酯酶（ChE）抑制剂梭曼的作用。梭曼浓度大于或等于1 nM时，可增加电场刺激引起的收缩幅度和衰减。对衰减的影响显著依赖于刺激频率，在3至60 Hz之间增加了2.4倍。梭曼还增强了浴槽中加入乙酰胆碱（ACh）引起的张力。对于由胆碱酯酶不水解的激动剂氨甲酰胆碱引起的收缩，几乎未观察到增强作用。梭曼浓度大于或等于3 nM时导致出现持续性挛缩。这些挛缩起病延迟，且与胆碱酯酶活性密切相关。丙基苯甲酰胆碱氮芥对毒蕈碱受体的烷基化作用拮抗了梭曼对自发和电诱发肌肉收缩的作用。结果与一种机制相符，即梭曼的毒性作用是由ChE活性受抑制继发神经释放的ACh蓄积介导的。这种蓄积的一个重要因素被认为是毒蕈碱受体对ACh从神经效应器接头处流出的缓冲作用。
