Discrimination of carboxylesterases of chicken neural tissue by inhibition with a neuropathic, non-neuropathic organophosphorus compounds and neuropathy promoter

New insights on molecular interactions of organophosphorus pesticides with esterases

“…The interest shown in esterases of the chicken nervous system using PV as a substrate are related with studies into OPIDN and promotion of OPIDN. Distribution of PV esterase activities sensitive to OPs was measured in brain, spinal cord and sciatic nerve in homogenate, soluble and particulate fractions in chicken (Escudero et al, 1995;1997a;1997b;Céspedes et al, 1997). To discriminate NTE from other PVases, two different assays were designed: a concurrent assay where paraoxon and mipafox together were incubated with the test compound (DFP, PMSF, or DFP), and a sequential assay where each inhibitor was added after the one before (Barril et al, 1999).…”

“…To discriminate NTE from other PVases, two different assays were designed: a concurrent assay where paraoxon and mipafox together were incubated with the test compound (DFP, PMSF, or DFP), and a sequential assay where each inhibitor was added after the one before (Barril et al, 1999). These early studies were able to discriminate at least four different carboxylesterases components in the brain membrane, six in the membrane spinal cord, six in the membrane sciatic nerve, three in the soluble brain fraction, five in the soluble spinal cord and four in the soluble fraction of chicken sciatic nerve (Céspedes et al, 1997;Escudero et al, 1997a;1997b;Estévez et al, 2004;.…”

Neuropathy Target Esterase

“…M-200 is a portion of the C activity (see Section 67.4.2), which can be segregated in assays in which the mipafox concentration is raised (from the 50 M used in standard assays) to detect an enzyme with a 20-min I 50 of 200 M (Lotti and Moretto, 1999;Milatovic et al, 1997). Vilanova and colleagues have also identified a component of soluble PV hydrolases that fits the characteristics of the target for promoters rather than initiators of OPIDN (Céspedes et al, 1997;Vilanova et al, 1999). However, although it seems likely that the target for promotion of OPIDN or other axonopathies is a serine esterase distinct from NTE, subsequent efforts to identify it have not been successful (Moretto et al, 2005(Moretto et al, , 2007.…”

Phenylmethylsulfonyl Fluoride, a Potentiator of Neuropathy, Alters the Interaction of Organophosphorus Compounds with Soluble Brain Esterases

“…18,19 It has been reported that given the chemical nature of the promoters, the target has to be an esterase similar to NTE and is, therefore, likely to hydrolyze the same substrate, i.e., phenyl valerate (PV), but is resistant to mipafox. 20,21 Other non-neuropathic NTE inhibitors, such as phenyl-N-methyl-Nbenzyl-carbamate and phenyl-n-pentyl-phosphinate, n-butyl sulfonyl fluoride, S-ethyl hexahydro-1H-azepine-1-carbothioate (molinate), S-4-chlorobenzyl diethylthiocarbamate (thiobencarb), and KBR-2822, have also been found to promote OPIDN. 12,22,18,23,24 It has been suggested that the target of promotion is embraced in a fraction which has been separated by molecular exclusion chromatography of the soluble fraction from the chick sciatic nerve called peak V 0 .…”

“…Several lines of evidence suggest that OPIDN promotion does not involve NTE, although all the promoters identified to date are NTE inhibitors . Only metamidophos ( O , S -dimethylphosphorothiomidate) and KBR 2822 ( O -(2-chloro-2,3,3 trifluorocyclobutyl) O -ethyl S -propyl phosphorothioate) promote OPIDN at doses causing marginal NTE inhibition. , It has been reported that given the chemical nature of the promoters, the target has to be an esterase similar to NTE and is, therefore, likely to hydrolyze the same substrate, i.e., phenyl valerate (PV), but is resistant to mipafox. , Other non-neuropathic NTE inhibitors, such as phenyl- N -methyl- N -benzyl-carbamate and phenyl- n -pentyl-phosphinate, n -butyl sulfonyl fluoride, S -ethyl hexahydro-1 H -azepine-1-carbothioate (molinate), S -4-chlorobenzyl diethylthiocarbamate (thiobencarb), and KBR-2822, have also been found to promote OPIDN. ,,,, It has been suggested that the target of promotion is embraced in a fraction which has been separated by molecular exclusion chromatography of the soluble fraction from the chick sciatic nerve called peak V 0 . , This fraction was first described by Escudero and co-workers in soluble esterases of the brain, spinal cord, and sciatic nerve. , …”