Abstract

The endogenous phosphorylation of specific brain proteins in white Leghorn laying hens treated with tri-o-cresyl phosphate (TOCP) with and without verapamil, a calcium channel blocker, which has been shown to ameliorate clinical signs and nervous lesions associated with organophosphate-induced delayed neuropathy (OPIDN), was determined. Verapamil was given im at the dose of 7 mg/kg/day for 4 days beginning 1 day before administration of TOCP (750 mg/kg, po). Phosphorylation of crude synaptosomal (P2) membrane proteins was assayedin vitrousing [γ-32P]ATP as a phosphate donor. Following resolution of brain membrane proteins by SDS-PAGE, specific protein phosphorylation was detected by autoradiography and quantified by densitometry TOCP caused, 21 days after dosing, an enhancement of the phosphorylation of membrane proteins with apparent molecular weights of 40, 55, and 60 kDa by as much as 253, 322, and 609%, respectively. Verapamil administered to TOCP-treated hens abolished the enhancement and even caused some inhibition. This indicates that calcium channel blocker may contribute to the amelioration of OPIDN by preventing the enhancement of phosphorylation of brain membrane proteins.

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