Activation of Phosphatidylinositol-linked Novel D1 Dopamine Receptor Contributes to the Calcium Mobilization in Cultured Rat Prefrontal Cortical Astrocytes
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Recent evidences indicate the existence of an atypical D1 dopamine receptor other than traditional D1 dopamine receptor in the brain that mediates PI hydrolysis via activation of phospholipase Cβ (PLCβ). To further understand the basic physiological function of this receptor in brain, the effects of a selective phosphoinositide (PI)-linked D1 dopamine receptor agonist SKF83959 on cytosolic free calcium concentration ([Ca2+]i) in cultured rat prefrontal cortical astrocytes were investigated by calcium imaging. The results indicated that SKF83959 caused a transient dose-dependent increase in [Ca2+]i. Application of D1 receptor, but not D2, α1 adrenergic, 5-HT receptor, or cholinergic antagonist prevented SKF83959-induced [Ca2+]i rise, indicating that activation of the D1 dopamine receptor was essential for this response. Increase in [Ca2+]i was a two-step process characterized by an initial increase in [Ca2+]i mediated by release from intracellular stores, supplemented by influx through voltage-gated calcium channels, receptor-operated calcium channels, and capacitative Ca2+ entry. Furthermore, SKF83959-stimulated increase in [Ca2+]i was abolished following treatment with a PLC inhibitor. Overall, these results suggested that activation of D1 receptor by SKF83959 mediates a dose-dependent mobilization of [Ca2+]i via the PLC signaling pathway in cultured rat prefrontal cortical astrocytes.
KeywordsSKF83959 Dopamine receptor Calcium Astrocyte Phospholipase C
This work was supported by grants from the National Science Foundation for the Distinguished Young Scientists in China (No. 30425024), the National Basic Research Program of China (973 Program) (No. 2007CB507404), the National Natural Science Foundation of China (No.30570556) to Dr. Jian-Guo Chen, and the Joint Research Fund for Overseas Chinese Young Scholars to Dr. Yong Xia and Dr. Jian-Guo Chen (No. 30728010).
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