Abstract |
Neuropathy target esterase (NTE) is suggested to be the molecular target for the initiation of the organophosphorus induced delayed polyneuropathy (OPIDP). O,O'- diethyl p-nitrophenyl phosphate ( paraoxon) was the non-neurotoxic OP of choice for the standard assay of NTE to block the non-relevant esterases (phenylvalerate hydrolases) because it was supposed not to inhibit the enzymic activity of the target protein while N,N'-diisopropyl phosphorodiamidofluoridate ( mipafox) is the neuropathic OP used to inhibit (and so to detect) NTE activity. A soluble form of NTE (S-NTE) had previously been described in peripheral nerve which showed a different inhibitor response from that of the particulate NTE (P-NTE). The use of a sequential type of inhibition protocol revealed the presence of an activity component within S-NTE which was extremely sensitive to different esterase inhibitors. Such a soluble activity component remained hidden under the usual concurrent inhibition procedure with paraoxon and was about one order of magnitude more sensitive than P-NTE to the inhibitors studied in the present article. Our results suggest that paraoxon could produce a strong reversible effect on S-NTE when the concurrent procedure is used so that it interferes with its inhibition by both neuropathy inducers and promoters. As a result S-NTE seems to be much more sensitive, than previously believed, to several esterase inhibitors involved in either the genesis of delayed polyneuropathy and/or axonopathy promotion.
|
Authors | J Barril, E Vilanova |
Journal | Chemico-biological interactions
(Chem Biol Interact)
Vol. 108
Issue 1-2
Pg. 19-25
(Dec 12 1997)
ISSN: 0009-2797 [Print] Ireland |
PMID | 9463518
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Biomarkers
- Enzyme Inhibitors
- Carboxylic Ester Hydrolases
- neurotoxic esterase
- Paraoxon
|
Topics |
- Animals
- Biomarkers
- Carboxylic Ester Hydrolases
(antagonists & inhibitors, drug effects, metabolism)
- Chickens
- Enzyme Inhibitors
(metabolism)
- Paraoxon
(toxicity)
- Peripheral Nervous System Diseases
(chemically induced)
- Sciatic Nerve
(drug effects, enzymology)
- Solubility
- Substrate Specificity
|