Novel protein targets for organophosphorus compounds.
Inhibition of tritiated di-isopropyl phosphorofluoridate labelling by a range of organophopshorus compounds was used to screen for novel OP-reactive targets in rat-brain homogenates. Analysis of target proteins was conducted by SDS/PAGE and detection of tritiated proteins using a thin layer chromatography (TLC) linear analyser. Two major sites of 3H-DFP labelling were found with relative molecular masses of 30 and 85 kDa. Rates of reaction of these labelling sites with a range of OP compounds were compared to that of acetylcholinesterase. The 30 kDa band was found to be more sensitive to paraoxon, dichlorvos and diazoxon than acetylcholinesterase. The 85 kDa band was found to be more sensitive to dichlorvos and diazoxon than acetylcholinesterase. Neither labelling band reacted with chlorfenvinphos or demeton-s-methyl at significant rates.
Medical Research Council Toxicology Unit, University of Leicester, UK.
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Richards
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Johnson
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Ray
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Walker
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D011232:Chemical Precipitation; D002855:Chromatography, Thin Layer; D006863:Hydrogen-Ion Concentration; D007531:Isoflurophate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D014316:Tritium
D009419:Nerve Tissue Proteins; D009943:Organophosphorus Compounds; D014316:Tritium; D007531:Isoflurophate; D002118:Calcium