氯化甲基汞在体外抑制脑毒蕈碱受体结合的恢复效应

为研究甲基汞对脑毒蕈碱（Ｍ）受体的影响及常用拮抗剂对甲基汞引起该受体特异结合抑制的恢复效应，应用放射性配体结合技术进行了体外试验。结果显示，甲基汞能明显抑制３Ｈ－二苯基羟乙酸奎宁酯（３Ｈ－ＱＮＢ）与脑Ｍ受体的特异结合，ＩＣ５０为４．８ｍｍｏｌ／Ｌ。巯基化合物二巯基丙磺酸钠，二巯基苏糖醇，谷胱甘肽及半胱氨酸能使甲基汞抑制的３Ｈ－ＱＮＢ的结合不同程度地恢复，而乙二胺四乙酸、亚硒酸钠则无这种恢复效应，表明甲基汞对脑Ｍ受体的影响是汞与受体上巯基基团相互作用的结果，而含有巯基的拮抗剂能与受体上巯基团结合的甲基汞竞争结合，从而恢复脑Ｍ受体与配体的结合能力。

Regeneration of Functionally Active Rat Brain Muscarinic Receptor in vitro After Inhibition with Methylmercury Chloride

The effect of methylmercury on muscarinic receptors and the regeneration of functionally active muscarinic receptor in vitro by antagonists were investigated. The result showed that methylmercury chloride (MMC) inhibited the binding of QNB to muscarinic receptor of rat brain lysed synaptosomes, with IC 50 values of 4.18mmol/L. Regeneration of functionally active rat brain muscarinic receptors after inhibition with methylmercury was achieved by 2,3 dimercapto 1 propanesulfonc acid, Na salt (DMPS) dithiothreitol (DTT), glutathione (GSH) and Cysteine. Blocking the sulfhydryl groups is suggested to be the molecular mechanism of inhibition of brain muscarinic receptors by methylmercury. Our results provide evidence that thiols chelate out mercuric cations that tightly bound to sulfhydryl groups in muscarinic receptor binding sites and regenerate 3H QNB binding activity.