BIOCHEMICAL-PROPERTIES AND POSSIBLE TOXICOLOGICAL SIGNIFICANCE OF VARIOUS FORMS OF NTE

NTE (neuropathy target esterase) is considered to be the target for organophosphorus-induced delayed polyneuropathy and is operationally measured by radiolabelling or by determining its esteratic activity as the paraoxon-resistant mipafox-sensitive phosphorylable site(s). From electrophoresis and density gradient centrifugation using radiolabelling techniques, several phosphorylable sites have been described in hen brain that are paraoxon-resistant mipafox-sensitive; however, only the majority electrophoresis band (155 kDa) shows properties related with the aging reaction. Kinetic criteria have also suggested two components of brain NTE (NTE(A) and NTE(B)). Most brain NTE is recovered in the particulate microsomal fraction and only about 1% in soluble fraction. In sciatic nerve about 50%/50% activity is recovered as soluble (S-NTE) or particulate (P-NTE) forms. A similar distribution were observed in hen, cat, rat and young chick. The fixed time inhibition curves show that P-NTE is more sensitive to mipafox, DFP and hexyl-DCP than S-NTE, while the reverse is true for methamidophos. P-NTE fits properly to one sensitive component while S-NTE fits better to two sensitive component models, except in the case of methamidophos. In vivo, significant differences in the inhibition or P- and S-NTE by mipafox were found only when using low non-neuropathic dosing. The possible significance of different NTE forms are discussed.