Aas P, Veiteberg T A, Fonnum F
Biochem Pharmacol. 1987 Apr 15;36(8):1261-6. doi: 10.1016/0006-2952(87)90079-7.
Acute and sub-acute inhalation exposure of rats to the organophosphorus compound soman (O-[1,2,2-trimethylpropyl]-methylphosphonofluoridate) reduced the contraction of the bronchial smooth muscle induced by cholinergic stimulation. Acute exposure to 8.51 mg/m3 of soman for 45 min (total dose of 383 mg X min/m3) inhibited the acetylcholinesterase (AChE) activity of the bronchial smooth muscle by 85% and reduced the contraction induced by ACh and carbachol by 70% and 80% respectively. In spite of the extensive inhibition of AChE and reduction in the contraction following cholinergic stimulation, there was no alteration of the binding capacity (Bmax) or the equilibrium dissociation constant (Kd) to [3H]-quinuclidinyl benzilate ([3H]-QNB) in the rat bronchi following such an acute exposure. After sub-acute exposure (40 hr) to 0.45-0.63 mg/m3 of soman (total dose of 1080-1519 mg X min/m3) there was a reduction in AChE-activity of 94% and in the contraction of the bronchial smooth muscle induced by ACh and carbachol of 70%. Furthermore, also a reduction of the binding capacity to [3H]-QNB of approximately 40% was observed. Following exposure to soman by both acute and sub-acute inhalation exposure there was an increase in the apparent affinity (pD2) to ACh in the bronchial smooth muscle, due to the extensive inhibition of the AChE-activity. Inhalation of soman also induced a substantial inhibition of the AChE-activity in the lung (86%), but somewhat smaller inhibition in the hippocampus (70%) and almost no inhibition in the neostriatum (19%). Moreover, it was only in the lung where sub-acute exposure to soman produced a reduction of the binding capacity to [3H]-QNB and the reduction was approximately 50%. The results therefore show that after sub-acute inhalation of a relatively low concentration of the AChE-inhibitor soman, alterations in the number of cholinergic receptors are only observed in the peripheral cholinergic nervous system.
大鼠急性和亚急性吸入有机磷化合物梭曼（O-[1,2,2-三甲基丙基]-甲基磷酰氟）可降低胆碱能刺激诱导的支气管平滑肌收缩。急性暴露于8.51 mg/m³的梭曼45分钟（总剂量为383 mg·min/m³）可使支气管平滑肌的乙酰胆碱酯酶（AChE）活性抑制85%，并使乙酰胆碱（ACh）和卡巴胆碱诱导的收缩分别降低70%和80%。尽管AChE受到广泛抑制且胆碱能刺激后收缩减少，但急性暴露后大鼠支气管中与[³H]-喹核醇基苯甲酸酯（[³H]-QNB）的结合能力（Bmax）或平衡解离常数（Kd）没有改变。亚急性暴露（40小时）于0.45 - 0.63 mg/m³的梭曼（总剂量为1080 - 1519 mg·min/m³）后，AChE活性降低94%，ACh和卡巴胆碱诱导的支气管平滑肌收缩降低70%。此外，还观察到与[³H]-QNB的结合能力降低约40%。急性和亚急性吸入暴露于梭曼后，由于AChE活性受到广泛抑制，支气管平滑肌对ACh的表观亲和力（pD2）增加。吸入梭曼还可使肺中的AChE活性受到显著抑制（86%），但海马体中的抑制作用稍小（70%），新纹状体中的抑制作用几乎没有（19%）。此外，只有在肺中，亚急性暴露于梭曼会使与[³H]-QNB的结合能力降低，降低幅度约为50%。因此，结果表明，在亚急性吸入相对低浓度的AChE抑制剂梭曼后，仅在外周胆碱能神经系统中观察到胆碱能受体数量的改变。
