Neurochemical Mechanism of Organophosphorus Compounds: Effect on Neuromembrane

摘要

Work over the past year has focussed on two major areas: 1) an attempt to identify an endogenous enzyme in brain capable of inactivating diisopropylfluorophosphate (DEP) and other organophosphorus compounds; and 2) effects of DFP on in vivo brain protein synthesis. In addition, we have begun a new project in which the effects of DFP administered in vivo on brain content of several endogenous opioid peptides is to be examined. The possibility of a DFP-inactivating enzyme in brain tissue was examined by incubating mouse brain homogenates and subcellular fractions with DFP under various conditions. DFP hydrolysis was followed indirectly, by testing the effects of supernatants to inhibit acetylcholinesterase (AChE). Our results suggest that the 100,000g supernatant of brain homogenate (S3) may contain a DFP-hydrolyzing enzyme, but further work is needed to establish this conclusion. The results in the brain protein synthesis study, which are still very preliminary, suggest that DFP does alter the synthesis of specific polypeptide species in brain. The study of the effect of DFP on endogenous opioid peptides has just begun; we are still perfecting the methodology.