Astrocytes, glial cells in the central nervous system, perform a multitude of homeostatic functions and are in constant bidirectional communication with neuronal cells, a concept named the tripartite synapse; however, their role in the dopamine homeostasis remains unexplored. The aim of this study was to clarify the pharmacological and molecular characteristics of dopamine transport in cultured cortical astrocytes of adult rats. In addition, we were interested in the expression of mRNA of dopamine transporters as well as dopamine receptors D1 and D2 and in the effect of dopaminergic drugs on the expression of these transporters and receptors. We have found that astrocytes possess both Na⁺-dependent and Na⁺-independent transporters. Uptake of radiolabelled dopamine was time-, temperature- and concentration-dependent and was inhibited by decynium-22, a plasma membrane monoamine transporter inhibitor, tricyclic antidepressants desipramine and nortriptyline, both inhibitors of the norepinephrine transporter. Results of transporter mRNA expression indicate that the main transporters involved in cortical astrocyte dopamine uptake are the norepinephrine transporter and plasma membrane monoamine transporter. Both dopamine receptor subtypes were identified in cortical astrocyte cultures. Twenty-four-hour treatment of astrocyte cultures with apomorphine, a D1/D2 agonist, induced upregulation of D1 receptor, norepinephrine transporter and plasma membrane monoamine transporter, whereas the latter was downregulated by haloperidol and L-DOPA. Astrocytes take up dopamine by multiple transporters and express dopamine receptors, which are sensitive to dopaminergic drugs. The findings of this study could open a promising area of research for the fine-tuning of existing therapeutic strategies.

中文翻译：

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参与成年大鼠皮质星形胶质细胞多巴胺摄取的转运蛋白：动力学、表达和药理学调节

星形胶质细胞是中枢神经系统中的神经胶质细胞，执行多种稳态功能，并与神经元细胞保持持续的双向通信，这一概念称为三方突触；然而，它们在多巴胺稳态中的作用仍未被探索。本研究的目的是阐明培养的成年大鼠皮质星形胶质细胞中多巴胺转运的药理学和分子特征。此外，我们对多巴胺转运蛋白以及多巴胺受体 D1 和 D2 的 mRNA 表达以及多巴胺能药物对这些转运蛋白和受体表达的影响感兴趣。我们发现星形胶质细胞同时具有Na ⁺依赖性和Na ⁺非依赖性转运蛋白。放射性标记的多巴胺的摄取具有时间、温度和浓度依赖性，并受到质膜单胺转运蛋白抑制剂 decynium-22、三环类抗抑郁药地昔帕明和去甲替林（两种去甲肾上腺素转运蛋白抑制剂）的抑制。转运蛋白mRNA表达结果表明，参与皮质星形胶质细胞多巴胺摄取的主要转运蛋白是去甲肾上腺素转运蛋白和质膜单胺转运蛋白。两种多巴胺受体亚型均在皮质星形胶质细胞培养物中得到鉴定。用阿扑吗啡（一种 D1/D2 激动剂）对星形胶质细胞培养物进行 24 小时处理，诱导 D1 受体、去甲肾上腺素转运蛋白和质膜单胺转运蛋白上调，而后者被氟哌啶醇和左旋多巴下调。星形胶质细胞通过多种转运蛋白吸收多巴胺并表达对多巴胺能药物敏感的多巴胺受体。这项研究的结果可能为现有治疗策略的微调开辟一个有前景的研究领域。