PHENYL VALERATE ESTERASES OTHER THAN NEUROPATHY TARGET ESTERASE AND THE PROMOTION OF ORGANOPHOSPHATE POLYNEUROPATHY

Certain esterase inhibitors (such as phenylmethanesulfonyl fluoride, P MSF) enhance the clinical and morphological signs of organophosphate-i nduced delayed polyneuropathy (OPIDP) in hens. This is called promotio n 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 tha n NTE. Brain and sciatic nerve PV esterases of hens were incubated wit h diisopropylphosphorofluoridate (DFP; 5 mu M) or N,N-diisopropyl phos phorodiamidofluoridate (mipafox; 50 mu M) to inhibit NTE and other est erases thought not to be relevant to promotion. Remaining activities, quantitatively similar after either inhibition, were titrated with PMS F (up to 500 mu M) and analysis of time course of inhibition showed fi rst-order kinetics. Mipafox (50 mu M)-resistant PMSF (500 mu M)-sensit ive activity (about 80% of mipafox-resistant ones) was tested both in vitro and in vivo with several inhibitors. No correlation was found be tween inhibition of mipafox-resistant PMSF-sensitive activity and the capability of several inhibitors to promote OPIDP. We conclude that th e target of promotion is unlikely to be a PV esterase resistant to mip afox (50 mu M).