INHIBITION OF HUMAN FETAL BRAIN ACETYLCHOLINESTERASE - MARKER EFFECT OF NEUROTOXICITY
INHIBITION OF HUMAN FETAL BRAIN ACETYLCHOLINESTERASE - MARKER EFFECT OF NEUROTOXICITY
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DOI：
10.1080/15287399109531527
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发表时间：
1991-01-01
期刊：
影响因子：
--
通讯作者：
BHATTACHARYA, S
中科院分区：
文献类型：
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作者：
BANERJEE, J;GHOSH, P;BHATTACHARYA, S
人类胎儿大脑是在妊娠 8-10 周后从知情患者处获得的。 在胎儿大脑中发现了明确的 AChE 区域化，小脑记录的活性最高，大脑半球的活性最低。 小脑 AChE 活性的最佳条件根据缓冲液的摩尔浓度、pH、温度和底物（乙酰硫胆碱碘化物）、活化剂（NaCl、MgCl2）和硫醇指示剂（二硫代双硝基苯甲酸）的浓度来确定。 将两种商业农药 Metacid-50（O,O-二甲基对硝基苯基硫代磷酸酯）和西维因（N-甲基萘基-1-氨基甲酸酯）对小脑 AChE 的体外抑制作用与纯抗胆碱酯酶药物进行比较，二异丙基氟磷酸盐比氨基甲酸酯化合物具有更大的神经毒性，与丝氨酸和西维因相比，DFP 和 Metacid-50 对 AChE 的抑制程度更高。 还采用体外AChE抑制动力学程序对精神药物进行了测定，发现精神药物的效力不如有机磷酸酯和氨基甲酸酯化合物。 结果表明，纯的和商业的有机磷酸酯、氨基甲酸酯和精神药物都能够显着改变 AChE 活性。 因此，母亲接触这些环境毒物可能会对胎儿的神经功能产生不利影响。
Human fetal brains were obtained after medical termination of pregnancy at 8-10 wk from informed patients. A definite regionalization of AChE was found in the brain of the fetus, with cerebellum recording the highest and cerebral hemisphere the lowest activity. Optimum conditions for the cerebellar AChE activity were determined with respect to molarity of the buffer, pH, temperature, and concentrations of substrate (acetylthiocholine iodide), activators (NaCl, MgCl2), and thiol indicator (dithiobisnitrobenzoic acid). In vitro inhibition of cerebellar AChE with two commercial pesticides, Metacid-50 (O,O-dimethyl p-nitrophenyl phosphorothioate) and carbaryl (N-methyl napthyl-1-carbamate), were compared with pure anticholinesterase agents, diisopropylfluorophosphate are more neurotoxic than carbamate compounds, as evidenced by higher degree of AChE inhibition by DFP and Metacid-50 as compared to eserine and carbaryl. Assays were also done with psychotropic drugs by employing the procedure of in vitro AChE inhibition kinetics, and it was found that psychotropic drugs are less potent than organophosphate and carbamate compounds. Results indicate that pure and commercial organophosphates and carbamates and psychotropic drugs are all able to significantly alter the AChE activity. Thus exposure of the mother to these environmental toxicants may adversely affect the fetal neural functions.