Species differences in brain acetylcholinesterase response to monocrotophos in vitro

Species-related differences in sensitivity to acute intoxication by anticholinesterase (anti-ChE) compounds have been attributed, in large part, to differences in the kinetics of inhibition of acetylcholinesterase (AChE: EC 3.1.1.7) in vitro. The following investigation was designed to determine if species-related differences in the sensitivity of brain AChE to inhibition by monocrotophos (MCP) could contribute to the interspecies differences in toxicity. Brain AChE activity was significantly greater in fish followed by pigeon and rat. MCP was found to be a competitive inhibitor of rat, pigeon, and fish brain AChE, thereby, altering the Km (Michaelis constant) widely among the species. Comparatively, least alterations in Km were observed in fish and maximum in pigeon. The Ki (bimolecular inhibition constant) of rat was 1.4- and 3.2-fold lower than that of pigeon and fish, respectively. Although fish brain had significantly greater AChE activity, it was the least sensitive to MCP inhibition. These data suggest that the greater sensitivity of rodent brain AChE to inhibition by MCP may contribute to the greater toxicity of MCP in rodents than in birds and fishes.