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锰对大鼠脑纹状体多巴胺受体的毒作用
Toxic action of manganese on dopamine receptors in rat striatum
【摘要】 大鼠每日ip15或30mg/kg硫酸锰,连续10d。末次染毒后24h,体重、脑重和纹状体重均未见变化。30mg/kg组,DNA,RNA降低,蛋白质/DNA比值明显增加;电镜下DA神经元个别线粒体肿胀。锰增加[~3H]spiperone与脑纹状体DA受体的特异性结合,同时亦看到染毒大鼠纹状体和突触中锰含量升高,提示脑纹状体DA受体功能状态与其锰含量变化有关。锰的中枢神经毒性表现来源于DA神经功能的损害。
【Abstract】 Rats were treated on 10 consecutive days with ip MnSO4 at 15 or 30 mg/kg. 24 h after the last dose, no significant differences in the body, brain, and striatum weights were observed between the control and Mn-treated rats. DNA or RNA decreased and protein/DNA ratio increased significantly in striatum in high Mn-treated rats but not in low Mn-treated rats. In high Mn-treated rats,swelling of some mitochondria was observed in the dopaminergic neuron under electronic microscope. The major increase in the binding of the dopaminergic antagonist [3H]spiperone to striatal analysis revealed that changes in both the dissociation constant (KD),which was significantly decreased in Mn-treated rats (from 4.32 nM to 3.67 nM) and in the receptor site density (Bmax),which was increased in Mn-treated rats (from 589 to 692 fmol/mg protein) . Manganese exposure produced a marked and dose-dependent increase in striatal and synaptic manganese, associated with a consistent elevated in the binding of the C3H3 spiperone to striated membranes. The presence of excess mangrncse in the striatum and synapses presumably leads to alteration in the function of dopaminergic receptor. The results suggested a sensitivity of dopaminergic pathway to manganese toxicity in the nervous system and an involvement of dopaminergic system in neurotoxicity of manganese.
【Key words】 manganese poisoning; dopamine receptors; [3H]spiperone; striatum; electron microscopy;
- 【文献出处】 中国药理学与毒理学杂志 ,Chinese Journal of Pharmacology and Toxicology , 编辑部邮箱 ,1987年02期
- 【被引频次】15
- 【下载频次】56