Acetylcholinesterase에 대한 유기인산제 농약의 억제작용과 Oxime에 의한 재활성작용에 관한 연구

Abstract

Cholinesterase in human blood cells and plasm'" are inhibited in varying degrees by organophosphorus: insecticides and nerve agents through phosphorylation The phosphorylated enzymes can often be reactivated by nucleophilic compounds such as oximes and hydroxamic acids provided conversion of inhibited enzyme to a nonreactive form(aging) has not occured In this work. the effects of organophosphorus insecticides (Parathion and PAP) on membrane-bound acetylcholinesterase from human erythrocyte ghosts were studied by using automatic recording spectrophotometer according to the method of Ellman et aL Also, the influence of the oxime upon reactivation was studied. 1. There was a concenturation dependent inhibition <>f acetylcholinesterase by parathion and PAP. The inhibition of acetylcholinesterase by PAP was shown to be more rapid and complete than that by para thion. 2. Decreasing the concenturation of 2-PAM below 정 x lO M resulted in incomplete reactivation. At therapeutical concenturation of 2-PAM, 82.6% of the enzyme activity was restored in parathion-inhibited 'enzyme , and 64.0% in PAP inhibited enzyme. 3. In vitro reactivation by 2-PAM of PAP inhibited cholinesterase was shown to be more difficult than that of paration-inhibited cholinesterase 4. Maximal reactivation of inhibited acetylcholinesterase was noted 30 minutes after addiction of 2 -PAM and thereafter the degree of reactivation decTeased. 5. No spontaneous reactivation was noticed during rthe time of the experiment It was concluded that the rate and ease of inhibition and reactivation are dependent on the bulk of the side chain(leaving group) , and the phosphorylated oximes may act as anticholinesterase.