Inhibition of calcium-stimulated ATPase in the hen brain P2 synaptosomal fraction by organophosphorus esters: Relevance to delayed neuropathy

Organophosphorus (OP) compounds have been reported to inhibit Ca/Mg-ATPase. bur the relevance of this inhibition to organophosphate-induced delayed ne uropathy (OPIDN) has nor been explored. To determine if inhibition of this enzyme was related to the development of OPIDN, neuropathic and nonneuropat hic OP compounds were tested for their ability to inhibit Ca-stimulated ATP ase activity in the P2 synaptosomal fraction from hen brain. Following in v itro exposure to 10(-3) to 10(-5) M OP compounds, Ca-stimulated ATPase acti vity was inhibited by chlorpyrifos, chlorpyrifos-oxon, phenyl saligenin pho sphate (PSP), and tri-o-tolyl phosphate (TOTP), but nor by parathion, parao xon, or diisopropyl fluorophosphate (DFP). Further investigation of inhibit ion induced by chlorpyrifos determined that inhibition was noncompetitive w ith respect to calcium and ATP. OP compound hydrophobicity was well correla ted with in vitro inhibition of Ca-stimulated ATPase, suggesting that OP co mpounds interact with membrane lipids, and this interaction may contribute to the noncompetitive inhibition of Ca-stimulated ATPase that was observed. Subsequent to in vivo exposure, DFP, but not PSP, produced inhibition of C a-stimulated ATPase activity in the hen brain P2 synaptosomal Fraction. The se data indicate that inhibition of Ca-stimulated ATPase activity is not co rrelated to neuropathic potential and demonstrate that inhibition of Ca/Mg- ATPase is not responsible for OPIDN.