The role of neurotoxic esterase (NTE) in the prevention and potentiation of organophosphorus-induced delayed neurotoxicity (OPIDN).
The first step in the initiation of organophosphorus-induced delayed neuropathy (OPIDN) is proposed to be the phosphorylation of an enzyme found in the nervous system called neurotoxic esterase (neuropathy target esterase, NTE). It has been known for over twenty years that non-neuropathic inhibitors of NTE exist and can actually prevent OPIDN when given before a neuropathic organophosphate (OP). Within the last three years it has become evident that another outcome is possible following in vivo interaction between neuropathic and nonneuropathic NTE inhibitors. When administered after OP exposure, nonneuropathic inhibitors can intensify or potentiate signs of OPIDN in adult chickens. Additionally, whereas developing chickens are typically resistant to the effects of neuropathic OPs, resistant age groups will develop OPIDN when exposure to a neuropathic OP is followed by the non-neuropathic NTE inhibitor phenylmethylsulfonyl fluoride. As in the case of prevention, studies of the potentiation of OPIDN may yield insight into mechanisms involved in the pathogenesis of delayed neurotoxicity. A brief review of current knowledge regarding the role of NTE in both the prevention and potentiation of OPIDN is presented.
Pope
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Division of Pharmacology and Toxicology, School of Pharmacy, Northeast Louisiana University, Monroe 71209.
Tanaka
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Padilla
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D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000502:physiology*; D002645:Chickens; D004357:Drug Synergism; D009422:Nervous System Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D009943:Organophosphorus Compounds / Q000633:toxicity*
D009943:Organophosphorus Compounds; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase