Effects of verapamil on brainstem microsomal protein phosphorylation in vitro in hens dosed with tri-o-cresyl phosphate

AIM: To examine if the calcium channel blocker, verapamil, would affect the level of brainstem microsomal protein phosphorylation after administration of tri-o-cresyl phosphate(TOCP), by which maybe indicate some clues to the pathogenesis of organophosphate-induced delayed polyneuropathy (OPIDP). METHODS: Verapamil(7 mg·kg^-1· d^-1, im) was given for 4 d (d 1 - d 4). A dose of TOCP (750 mg·kg^-1) was administrated by ig on d 2. Phosphorylation of brainstem microsomal proteins was assayed in vitro by using [γ-³²P] ATP as phosphate donor. Radiolabeled proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and visualized by autoradiography. The changes of the protein phosphorylation were quantified by densitometry. RESULTS: TOCP administration enhanced the phosphorylation of the microsomal proteins with apparent molecular weights of 45, 41, 32 ku by 119%, 174%, 173%, respectively. Verapamil abolished the enhancement induced by TOCP. CONCLUSION: The mechanism of calcium channel blocker to ameliorate organophosphate-induced delayed polyneuropathy might be the protection of the brainstem microsomal proteins from enhancement of phosphorylation.