Liu Jue, Wang Fang, Huang Chao, Long Li-Hong, Wu Wen-Ning, Cai Fei, Wang Jiang-Hua, Ma Li-Qun, Chen Jian-Guo
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, Hubei, 430030, China.
Cell Mol Neurobiol. 2009 May;29(3):317-28. doi: 10.1007/s10571-008-9323-9. Epub 2008 Oct 31.
Recent evidences indicate the existence of an atypical D(1) dopamine receptor other than traditional D(1) dopamine receptor in the brain that mediates PI hydrolysis via activation of phospholipase C(beta) (PLC(beta)). To further understand the basic physiological function of this receptor in brain, the effects of a selective phosphoinositide (PI)-linked D(1) dopamine receptor agonist SKF83959 on cytosolic free calcium concentration (Ca(2+)) in cultured rat prefrontal cortical astrocytes were investigated by calcium imaging. The results indicated that SKF83959 caused a transient dose-dependent increase in Ca(2+). Application of D(1) receptor, but not D(2), alpha(1) adrenergic, 5-HT receptor, or cholinergic antagonist prevented SKF83959-induced Ca(2+) rise, indicating that activation of the D(1) dopamine receptor was essential for this response. Increase in Ca(2+) was a two-step process characterized by an initial increase in Ca(2+) mediated by release from intracellular stores, supplemented by influx through voltage-gated calcium channels, receptor-operated calcium channels, and capacitative Ca(2+) entry. Furthermore, SKF83959-stimulated increase in Ca(2+) was abolished following treatment with a PLC inhibitor. Overall, these results suggested that activation of D(1) receptor by SKF83959 mediates a dose-dependent mobilization of Ca(2+) via the PLC signaling pathway in cultured rat prefrontal cortical astrocytes.
最近的证据表明，大脑中存在一种不同于传统D(1)多巴胺受体的非典型D(1)多巴胺受体，它通过激活磷脂酶C(β)(PLC(β))介导磷脂酰肌醇(PI)水解。为了进一步了解该受体在大脑中的基本生理功能，通过钙成像研究了选择性磷酸肌醇(PI)偶联的D(1)多巴胺受体激动剂SKF83959对培养的大鼠前额叶皮质星形胶质细胞胞质游离钙浓度([Ca(2+)]i)的影响。结果表明，SKF83959引起[Ca(2+)]i呈剂量依赖性短暂升高。应用D(1)受体拮抗剂而非D(2)、α(1)肾上腺素能、5-羟色胺受体或胆碱能拮抗剂可阻止SKF83959诱导的[Ca(2+)]i升高，表明D(1)多巴胺受体的激活对该反应至关重要。[Ca(2+)]i升高是一个两步过程，其特征是最初由细胞内钙库释放介导的[Ca(2+)]i升高，随后通过电压门控钙通道、受体操纵性钙通道和容量性Ca(2+)内流进行补充。此外，用PLC抑制剂处理后，SKF83959刺激的[Ca(2+)]i升高被消除。总体而言，这些结果表明，SKF83959激活D(1)受体通过PLC信号通路介导培养的大鼠前额叶皮质星形胶质细胞中[Ca(2+)]i的剂量依赖性动员。
