Toxicology Letters, 15 (1983) 13-17 Blsevier Biomedical Press 13 PARTIAL CHARACTERIZATION OF NEUROTOXIC ESTERASE OF HUMAN PLACENTA (Organophosphorus; delayed neurotoxicity; axonopathy) PAUL. E. GURBA and RUDY J. RICHARDSON* zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR Toxicology ResearchLaboratory, Department of Environmental and IndustrialHealth, School of Public He&h, The ~miversity of Michigan, Arm Arbor, MI 48109 fU.S.A.j (Received April ZSth, 1982) (Accepted July Sth, 1982) SUMMARY Neurotoxic esterase (NTE), the putative target far organophosphorus-induced delayed axonopathy, has been found in preparations of human placenta. The activity was primarily found in membrane- enriched fractions rather than high-speed supernatant. NTE was solubilized from a mixture of mitochon- drial and microsomal membranes with Triton X-100. The crude and solubilized activities had inhibitor characteristics similar to preparations from avian brain. Because of the similarities to NTE from brain and ready availability, human placenta may be an ideal source for the bulk purification of a human form of the enzyme. INTRODUCTION Delayed, distal axonopathy produced by organosphosphorus compounds such as tri-o-cresyl phosphate, diisopropylphosphofluoridate, and i’V,N’-diisopropylphos- phorodi~ido~uoridate (mipafox) is believed to be initiated by the inhibition and subsequent aging of a membrane protein called NTE [l]. Although initial studies of NTE have been conducted with chicken brain 111,NTE has been found in the neural tissue of a large number of different vertebrates [2]. Recently NTE has been found in non-neural tissues such as avian splenic and circulating lymphocytes [3], and human leukocytes [4]. To better understand the function of NTE and its relationship with the delayed neuropathy, we have been engaged in subcellular fractionation [S] and solubili~tion *To whom any correspondence should be directed. Abbreviations: BSA, bovine serum albumin; NTE, neurotoxic esterase; PV, phenyl valerate. 0378-4274/83/WOO-0000/$03.00 0 Elsevier Biomedical Press