Considerable evidence exists suggesting that the so-called neuropathy target esterase (NTE) is involved in the mechanisms responsible for organophosphorus-induced delayed polyneuropathy (OPIDP). Earlier studies in the adult hen, the habitually employed experimental model in OPIDP, have shown that most NTE activity in the brain is centered in particulate fractions, whereas approximately 50% of this activity in the sciatic nerve is encountered in soluble form, with the rest being particulate NTE. In the present work, we have studied the particulate and soluble fractional distribution of paraoxon-resistant phenylvalerate esterase activity (B activity), paraoxon- and mipafox-resistant phenylvalerate esterase activity (C activity), and NTE activity (B-C) according to ultracentrifugation criteria (100,000 g for 1 h). To this effect, two sensitive (adult hen and cat) and two scarcely sensitive (rat and chick) models were used. In all four experimental models, the distribution pattern was qualitatively similar: B activity and total NTE were much greater in brain (900-2,300 nmol/min/g of tissue) than in sciatic nerve (50-100 nmol/min/g of tissue). The proportion of soluble NTE in brain was very low (< 2%), whereas its presence in sciatic nerve was substantial (30-50%). The NTE/B ratio in brain was high for the particulate fraction (> 60%) and low in the soluble fraction (7-30%); in sciatic nerve the ratio was about 50% in both fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

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Neuropathy target esterase (NTE) is the proposed target site for the mechanism of initiation of the so-called organophosphorus-induced delayed polyneuropathy (OPIDP). NTE is operationally defined in this article as the phenylvalerate esterase activity which is resistant to inhibition by 40 microM paraoxon and sensitive to 250 microM mipafox. Soluble (S-NTE) and particulate (P-NTE) forms of NTE had first been identified in hen sciatic nerve [E. Vilanova, J. Barril, V. Carrera, and M. C. Pellín (1990). J. Neurochem., 55, 1258-1265]. P-NTE and S-NTE showed different sensitivities to the inhibition by several organophosphorus compounds over a range of inhibitor concentrations for a 30 or 120 minute fixed inhibition time at 37 degrees C. S-NTE was less sensitive to the inhibition by O,O'-diisopropyl phosphorofluoridate (DFP), hexyl 2,5-dichlorophenyl phosphoramidate (H-DCP), and mipafox than P-NTE and brain NTE, while the opposite was true for O,S-dimethyl phosphoroamidothioate (methamidophos). For each of the four inhibitors assayed, S-NTE showed two components of different sensitivity according to the inhibition curves fitted with exponential models. However, the inhibition of P-NTE by mipafox, DFP, and HDCP did not show the presence of a considerable proportion of a second component. The kinetics of heat inactivation showed that P-NTE inactivated faster and to a greater extent than S-NTE. It is concluded that (1) sciatic nerve S-NTE is more different from brain NTE than P-NTE; (2) P-NTE and S-NTE have different sensitivities to the inhibition by the studied organophosphorous compounds; (3) the inhibition curves suggest that S-NTE has two different enzymatic components while these are not so evident for P-NTE.