Direct effect of VX and soman on nicotinic receptors

O-ethyl-S-(2-diisopropylamino-ethyl)methylphosphonothiolate (VX) at 0.1-1 mmol/L was found to block the binding of 125I-cobrotoxin and [3H]Ach to nicotinic cholinergic receptors from electric organ of torpedo Narcine timilei. [35S]VX and [3H]VX were bound to the receptors and were displaced with 0.1 mmol/L cobrotoxin. Release of 22Na+ from receptor-rich membrane vesicles was caused by 1 mmol/L VX. In constrast, 1 mmol/L soman had little or no effect on the binding o f125I-cobrotoxin or [3H]Ach. [3H]soman did not show specific binding to the receptors. The phenomenon of desensitization was exhibited by preincubation of the receptors with carbamoylcholine but not VX or soman. These binding studies suggest that VX might have primarily direct effect on nicotinic receptors.