Zhou Li, Zhang Yixi, Shi Nian
Department of Toxicology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2002 Dec;20(6):405-8.
To explore the inhibitory effects of highly toxic organophosphorus compound and its substitute (methamidophos and acephate) on acetylcholinesterase (AChE) and their toxic mechanisms.
Ellman method was used to measure AChE activity in vitro and vivo.
Acephate and methamidophos could directly inhibit AChE activities in human erythrocyte membrane and rat brain synatosomal membrane in dose- and time-dependent manners in vitro, and this effect was irreversible. The IC50 of acephate and methamidophos affecting human erythrocyte membrane and rat synatosomal membrane were approximately 10(-4) mol/L and 10(-5) mol/L respectively and the Ki were 10(2) mol.L-1.min-1 and 10(3) mol.L-1.min-1 respectively. In vivo, after rats being administered with them for 5 d, the inhibitory rate of AChE activities in blood were increased to 68.24% and 54.80% respectively. When rats being administrated with acephate, there was 31.68% of inhibition on the brain stem, but no significant inhibition in other brain region was noticed, while methamidophos had a strong inhibitory effect on the activity of AChE in all brain regions, especially the cerebellum and brain-stem(71.51% and 61.85% respectively).
Acephate and methamidophos could directly inhibit the AChE activities in vitro, but the inhibition degree was different. In vivo, both could also inhibit AChE activities in blood. The difference in inhibition on brain regions may be one of the reason of various toxic effect of them.
探讨高毒有机磷化合物及其替代品（甲胺磷和乙酰甲胺磷）对乙酰胆碱酯酶（AChE）的抑制作用及其毒性机制。
采用Ellman法测定体外和体内的AChE活性。
体外实验中，乙酰甲胺磷和甲胺磷可剂量和时间依赖性地直接抑制人红细胞膜和大鼠脑突触体膜中的AChE活性，且这种作用是不可逆的。乙酰甲胺磷和甲胺磷对人红细胞膜和大鼠突触体膜的IC50分别约为10^(-4)mol/L和10^(-5)mol/L，Ki分别为10^(2)mol·L^(-1)·min^(-1)和10^(3)mol·L^(-1)·min^(-1)。体内实验中，大鼠经5天给药后，血液中AChE活性的抑制率分别升至68.24%和54.80%。给予乙酰甲胺磷时，对脑干有31.68%的抑制作用，但在其他脑区未观察到明显抑制，而甲胺磷对所有脑区的AChE活性均有较强抑制作用，尤其是小脑和脑干（分别为71.51%和61.85%）。
乙酰甲胺磷和甲胺磷在体外可直接抑制AChE活性，但抑制程度不同。在体内，二者也均可抑制血液中的AChE活性。对脑区抑制作用的差异可能是它们产生不同毒性作用的原因之一。
