D3 Dopamine Receptor Directly Interacts With D1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells
D3 Dopamine Receptor Directly Interacts With D1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells
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DOI：
10.1161/01.hyp.0000199983.24674.83
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发表时间：
2006-03
期刊：
影响因子：
8.3
通讯作者：
C. Zeng;Z. Wang;Hewang Li;P. Yu;S. Zheng;Li-juan Wu;L. Asico;U. Hopfer;G. Eisner;R. Felder;P. Jose
中科院分区：
文献类型：
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作者：
C. Zeng;Z. Wang;Hewang Li;P. Yu;S. Zheng;Li-juan Wu;L. Asico;U. Hopfer;G. Eisner;R. Felder;P. Jose
D3受体与D1受体协同作用抑制钠在肾近端小管中的转运；然而，发生这种情况的机制尚不清楚。由于多巴胺受体亚型可以相互调节和相互作用，我们研究了D3和D1受体在大鼠肾近端小管（RPT）细胞中的相互作用。D3激动剂PD128907呈浓度依赖性和时间依赖性增加D1受体的免疫反应性表达；这些作用被D3拮抗剂U99194A阻断。PD128907也能瞬时（15分钟）增加细胞膜D1受体的数量。激光共聚焦免疫荧光显微镜显示，Wistar-Kyoto大鼠RPT细胞中D3受体和D1受体的共定位比自发性高血压大鼠（SHRs）更明显。此外，D3和D1受体可以共免疫沉淀，并且在Wistar-Kyoto大鼠中D3受体激动剂刺激24小时后这种相互作用增加，而在SHRs中则没有。我们提出D3和D1受体的协同作用可能是由D3受体介导的总增加以及细胞表面膜D1受体的表达，以及D3和D1受体的直接相互作用引起的，这两者在SHRs中都受到损害。
D3 receptors act synergistically with D1 receptors to inhibit sodium transport in renal proximal tubules; however, the mechanism by which this occurs is not known. Because dopamine receptor subtypes can regulate and interact with each other, we studied the interaction of D3 and D1 receptors in rat renal proximal tubule (RPT) cells. The D3 agonist PD128907 increased the immunoreactive expression of D1 receptors in a concentration- and time-dependent manner; these effects were blocked by the D3 antagonist U99194A. PD128907 also transiently (15 minutes) increased the amount of cell surface membrane D1 receptors. Laser confocal immunofluorescence microscopy showed that D3 receptor and D1 receptor colocalized in RPT cells more distinctly in Wistar-Kyoto rats than in spontaneously hypertensive rats (SHRs). In addition, D3 and D1 receptors could be coimmunoprecipitated, and this interaction was increased after D3 receptor agonist stimulation for 24 hours in Wistar-Kyoto rats but not in SHRs. We propose that the synergistic effects of D3 and D1 receptors may be caused by a D3 receptor–mediated increase in total, as well as cell surface membrane D1 receptor expression, and direct D3 and D1 receptor interaction, both of which are impaired in SHRs.