Peripheral nerve soluble esterases are spontaneously reactivated after inhibition by paraoxon: implications for a new definition of neuropathy targetesterase

Soluble extracts of chicken peripheral nerve contain detectable amounts of phenyl valerate esterase (PVase) activity (about 2000 nmol/min per g of fre sh tissue). More than 95% of this activity is inhibited in assays where sub strate has been added to a preincubated mixture of tissue with the non-neur opathic organophosphorus compound (OP) paraoxon (O,O'-diethyl p-nitrophenyl phosphate): residual activity includes soluble neuropathy target esterase (SNTE) which, by definition, is considered resistant to long-term progressi ve (covalent) inhibition by paraoxon. However we have previously shown that paraoxon strongly interacts with S-NTE so interfering with its sensitivity to other inhibitors. We now show that, surprisingly, removal of paraoxon b y ultrafiltration ('P' tissue) in order to avoid such an interference resul ts in the reappearance of about 65% of total original soluble PVase activit y which is inhibited in the presence of this OF. Although a purely reversib le non-progressive inhibition might be suspected, kinetic analysis data sho w a time-progressive inhibition which suggests that such PVase(s) covalentl y bind paraoxon. Also a time-dependent recovery due to spontaneous reactiva tion of the PVase activity was observed after dilution of the inhibitor. Ge l filtration chromatography of 'P' tissue in Sephacryl S-300 shows that the reactivated activity is associated with proteins of about 100-kDa mass whi ch include S-NTE and an, as yet, unknown number of other PVases. The implic ations of these findings in the definition of NTE in a target tissue for th e so-called organophosphorus-induced delayed polyneuropathy (OPIDP) are dis cussed. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.