Johnson J A, Wallace K B
Toxicol Appl Pharmacol. 1987 Apr;88(2):234-41. doi: 10.1016/0041-008x(87)90009-3.
Interspecies comparisons indicate that fish are relatively more resistant to acute intoxication with parathion and paraoxon than are rodents. In contrast, fish are more sensitive to malathion and malaoxon. The following investigation was designed to determine if species-related differences in the sensitivity of brain acetylcholinesterase (AChE) to inhibition by paraoxon and malaoxon could contribute to the interspecies differences in toxicity. Brain AChE activity was significantly greater in fathead minnows and rainbow trout than in rats and mice. The fathead minnow and rainbow trout IC50 values for paraoxon were 228- to 1879-fold greater than the corresponding values for rat and mouse. Similarly, the Ki (bimolecular inhibition constant) was 159- to 1663-fold greater in rodents than in fish, which reflected both a higher KA (association constant) and kp (phosphorylation constant) in rodents. The rodent IC50 values for malaoxon were 30-80% that of the fish IC50, and the Ki was 30-50% greater in rodents than in fish. These data suggest that the greater sensitivity of rodent brain AChE to inhibition by paraoxon may contribute to the greater toxicity of parathion and paraoxon in rodents than in fish. In contrast, the lack of correlation between the inhibition of brain AChE by malaoxon and species-related differences in acute I D50 suggests that other factors, such as the limited carboxylesterase activity in fish, may be responsible for this species selectivity.
种间比较表明，与啮齿动物相比，鱼类对硫磷和对氧磷的急性中毒相对更具抵抗力。相比之下，鱼类对马拉硫磷和马拉氧磷更敏感。以下研究旨在确定脑乙酰胆碱酯酶（AChE）对氧磷和马拉氧磷抑制敏感性的种间差异是否可能导致毒性的种间差异。黑头呆鱼和虹鳟鱼的脑AChE活性显著高于大鼠和小鼠。黑头呆鱼和虹鳟鱼对氧磷的半数抑制浓度（IC50）值比大鼠和小鼠的相应值高228至1879倍。同样，双分子抑制常数（Ki）在啮齿动物中比在鱼类中高159至1663倍，这反映了啮齿动物中更高的结合常数（KA）和磷酸化常数（kp）。啮齿动物对马拉氧磷的IC50值是鱼类IC50值的30 - 80%，且啮齿动物的Ki比鱼类高30 - 50%。这些数据表明，啮齿动物脑AChE对氧磷抑制的更高敏感性可能导致硫磷和对氧磷在啮齿动物中比在鱼类中具有更大的毒性。相比之下，马拉氧磷对脑AChE的抑制与急性半数致死剂量（LD50）的种间差异之间缺乏相关性，这表明其他因素，如鱼类中有限的羧酸酯酶活性，可能是造成这种物种选择性的原因。
