Protease activity in brain, nerve, and muscle of hens given neuropathy-inducing organophosphates and a calcium channel blocker.
Activity of calcium-activated neutral protease (CANP or calpain), an enzyme responsible for degradation of axonal and muscle cytoskeletal elements, was determined in brain, sciatic nerve, and gastrocnemius muscle of hens given tri-ortho-tolyl phosphate (TOTP, 360 mg/kg po) or active congener phenyl saligenin phosphate (PSP, 2.5 mg/kg im) with and without a calcium channel blocker which ameliorated clinical signs of organophosphate-induced delayed neuropathy (nifedipine 1 mg/kg/day x 5). Calcium channel blocker administration was initiated 1 day prior to administration of organophosphate (OP). OP administration caused an increase in CANP activity in brain within 4 days and in sciatic nerve and gastrocnemius muscle within 2 days of administration. This increase did not occur if nifedipine was administered to PSP-treated hens. Total sciatic nerve calcium concentrations were also increased by PSP, but not until OP-treated hens were no longer being administered calcium blockers. This indicates that calcium channel blockers may contribute to amelioration of organophosphate-induced delayed neuropathy by attenuation of calcium-mediated disruption of axonal and muscle cytoskeletal homeostasis.
el-Fawal
H A
HA
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061.
Correll
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L
Gay
L
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Ehrich
M
M
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002154:Calpain / Q000032:analysis*; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D002645:Chickens; D003408:Cresols / Q000633:toxicity*; D005260:Female; D009132:Muscles / Q000201:enzymology*; D009543:Nifedipine / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000201:enzymology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology; D014317:Tritolyl Phosphates / Q000633:toxicity*
D003408:Cresols; D014317:Tritolyl Phosphates; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002154:Calpain; D009543:Nifedipine; C025541:tri-o-cresyl phosphate