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In vitro exposure to ambient fine and ultrafine particles alters dopamine uptake and release, and D2 receptor affinity and signaling.
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-09-14 , DOI: 10.1016/j.etap.2020.103484
María-de-Los-Angeles Andrade-Oliva 1 , Juan Escamilla-Sánchez 1 , Yazmín Debray-García 2 , Russell A Morales-Rubio 3 , Raúl González-Pantoja 1 , Marisela Uribe-Ramírez 3 , Omar Amador-Muñoz 4 , Raúl V Díaz-Godoy 5 , Andrea De Vizcaya-Ruiz 3 , José-Antonio Arias-Montaño 1
Affiliation  

The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson’s disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D2 receptor (D2R) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [3H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned D2Rs. FP and UFP collected from the air of Mexico City inhibited [3H]-dopamine uptake and increased depolarization-evoked [3H]-dopamine release in striatal synaptosomes. FP and UFP also enhanced D2R affinity for dopamine in membranes from either rat striatum or CHO-K1 cells transfected with the long isoform of the human D2R (hD2LR)2LR). In CHO-K1-hD2L In CHO-K1-hD2LR cells or striatal slices, FP and UFP increased the potency of dopamine or the D2R agonist quinpirole, respectively, to inhibit forskolin-induced cAMP formation. The effects were concentration-dependent, with UFP being more potent than FP. These results indicate that FP and UFP directly affect dopaminergic transmission.



中文翻译:

体外暴露于环境细颗粒和超细颗粒会改变多巴胺的吸收和释放以及D2受体的亲和力和信号传导。

暴露于环境污染物中,例如细颗粒和超细颗粒(FP和UFP),与帕金森氏病,抑郁症和精神分裂症以及与多巴胺能传播改变有关的疾病的风险增加有关。纹状体是具有大量多巴胺能传入神经的神经核,是颗粒毒性的靶位,其导致氧化应激,炎症,星形胶质细胞活化以及多巴胺含量和D 2受体(D 2 R)密度的改变。在这项研究中,我们评估了FP和UFP暴露对多巴胺能传播的体外影响,方法是评估[ 3H]-多巴胺被大鼠纹状体分离的神经末梢(突触小体)摄取和释放,以及天然和克隆的D 2 R亲和力和信号传导的修饰。从墨西哥城的空气中收集的FP和UFP抑制了纹状体突触体中[ 3 H]-多巴胺的摄取,并增加了去极化诱发的[ 3 H]-多巴胺的释放。FP和UFP还增强了大鼠纹状体或被人D 2 R(hD 2L R)2LR长异构体转染的CHO-K1细胞膜中多巴胺对D 2 R的亲和力。在CHO-K1-hD2L中在CHO-K1-hD 2L R细胞或纹状体切片中,FP和UFP增加了多巴胺或D 2的效力。R激动剂喹吡罗分别抑制福斯高林诱导的cAMP的形成。效果是浓度依赖性的,UFP比FP更有效。这些结果表明FP和UFP直接影响多巴胺能传播。

更新日期:2020-10-17
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