Distribution of neurotoxic esterase activity in the brain of control and diisopropyl phosphorofluoridate-treated hens: in vivo and in vitro exposure.
Neurotoxic esterase (NTE) is a protein which is hypothesized to be the site where certain organophosphorus compounds act to produce delayed-onset neurotoxicity. Adult white Leghorn hens (Gallus domesticus) were injected subcutaneously (0.5 mg/kg and 2.0 mg/kg) with diisopropyl phosphorofluoridate (DFP). Control and DFP-treated hens were killed 24 h after treatment and their brains sectioned into telencephalic, cerebellar, diencephalic, mesencephalic, metencephalic tegmentum, and myelencephalic portions. NTE activity was highest in the telencephalon and cerebellum, and brainstem activity progressively decreased moving caudally with the myelencephalon approaching reported spinal cord levels. Percent inhibition of NTE by DFP (0.5 mg/kg and 2.0 mg/kg) did not differ among brain regions or whole brain. The IC50's for DFP were not significantly different either among brain regions or whole brain. The results suggest that nervous system regions with higher NTE levels are protected from delayed neuropathy by virtue of overabundant NTE activity.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002645:Chickens; D004347:Drug Interactions; D005260:Female; D006868:Hydrolysis; D007279:Injections, Subcutaneous; D007531:Isoflurophate / Q000031:analogs & derivatives* / Q000633:toxicity; D010261:Paraoxon / Q000633:toxicity*; D010830:Physostigmine / Q000494:pharmacology
D007531:Isoflurophate; C005238:mipafox; D001285:Atropine; D010830:Physostigmine; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D010261:Paraoxon