Paper Report for: Milatovic_1997_Chem.Res.Toxicol_10_1045

Certain esterase inhibitors (such as phenylmethanesulfonyl fluoride, PMSF) enhance the clinical and morphological signs of organophosphate-induced delayed polyneuropathy (OPIDP) in hens. This is called promotion of OPIDP. The target of promotion is unknown, but it is likely to be different from neuropathy target esterase (NTE), the target of OPIDP, NTE is a neural phenyl valerate (PV) esterase, operationally defined by selective inhibition with organophosphates. This study was aimed to ascertain whether the target for promotion is a PV esterase other than NTE. Brain and sciatic nerve PV esterases of hens were incubated with diisopropylphosphorofluoridate (DFP; 5 microM) or N,N-diisopropyl phosphorodiamidofluoridate (mipafox; 50 microM) to inhibit NTE and other esterases thought not to be relevant to promotion. Remaining activities, quantitatively similar after either inhibition, were titrated with PMSF (up to 500 microM) and analysis of time course of inhibition showed first-order kinetics. Mipafox (50 microM)-resistant PMSF (500 microM)-sensitive activity (about 80% of mipafox-resistant ones) was tested both in vitro and in vivo with several inhibitors. No correlation was found between inhibition of mipafox-resistant PMSF-sensitive activity and the capability of several inhibitors to promote OPIDP. We conclude that the target of promotion is unlikely to be a PV esterase resistant to mipafox (50 microM).