Costa L G, Shao M, Basker K, Murphy S D
Chem Biol Interact. 1984 Mar;48(3):261-9. doi: 10.1016/0009-2797(84)90139-x.
Male rats were treated for 10 days with the organophosphorus insecticide, acetylcholinesterase inhibitor, O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate (disulfoton, 2 mg/kg/day by gavage). At the end of the treatment, binding of [3H]quinuclidinyl benzilate ( [3H]QNB) to cholinergic muscarinic receptors and cholinesterase (ChE) activity were assayed in the pancreas. Functional activity of pancreatic muscarinic receptor was investigated by determining carbachol-stimulated secretion of alpha-amylase in vitro. ChE activity and [3H]QNB binding were significantly decreased in the pancreas from disulfoton-treated rats. The alteration of [3H]QNB binding was due to a decrease in muscarinic receptor density with no change in the affinity. Basal secretion of amylase from pancreas in vitro was not altered, but carbachol-stimulated secretion was decreased. The effect appeared to be specific since pancreozymin was able to induce the same amylase release from pancreases of control and treated rats. The results suggest that repeated exposures to sublethal doses of an organophosphorus insecticide lead to a biochemical and functional alteration of cholinergic muscarinic receptors in the pancreas.
雄性大鼠用有机磷杀虫剂、乙酰胆碱酯酶抑制剂O,O - 二乙基S - [2 - (乙硫基)乙基]二硫代磷酸酯（乙拌磷，通过灌胃给予，剂量为2毫克/千克/天）处理10天。在处理结束时，测定胰腺中[3H]喹核醇基苯甲酸酯（[3H]QNB）与胆碱能毒蕈碱受体的结合以及胆碱酯酶（ChE）活性。通过测定体外卡巴胆碱刺激的α - 淀粉酶分泌来研究胰腺毒蕈碱受体的功能活性。在乙拌磷处理的大鼠胰腺中，ChE活性和[3H]QNB结合显著降低。[3H]QNB结合的改变是由于毒蕈碱受体密度降低，而亲和力未改变。体外胰腺淀粉酶的基础分泌未改变，但卡巴胆碱刺激的分泌减少。由于促胰液素能够诱导对照大鼠和处理大鼠胰腺释放相同的淀粉酶，所以该效应似乎具有特异性。结果表明，反复接触亚致死剂量的有机磷杀虫剂会导致胰腺中胆碱能毒蕈碱受体发生生化和功能改变。
