Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells
Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells
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DOI：
10.1152/ajprenal.90336.2008
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发表时间：
2008-10-01
影响因子：
4.2
通讯作者：
Aperia, Anita
中科院分区：
文献类型：
--
作者：
Khan, Farah;Spicarova, Zuzana;Aperia, Anita
钠排泄受多巴胺（作用于D1样受体（D1 R））和血管紧张素II（作用于AT（1）受体（AT 1 R））的双向调节。由于钠排泄必须在短时间内以很高的精度进行调节，因此我们测试了激动剂结合对肾近端小管细胞中D1 R-AT 1 R复合物内的相互受体功能的短期影响。大鼠肾近端小管细胞暴露于D1激动剂，发现导致快速部分内化的AT 1 R和AT 1 R信号的完全废除。类似地，大鼠近端小管细胞和肾组织暴露于血管紧张素II导致D1 R的快速部分内化和D1 R信号传导的废除。D1 R和AT 1 R，通过使用免疫共沉淀研究和谷胱甘肽-S-转移酶下拉试验，显示出在多蛋白复合物的合作伙伴。Na+-K+-ATP酶，这两种受体的目标，被包括在这个复合物中，和一个区域中的COOH末端尾的D1 R（残基397-416）被发现与AT 1 R和Na+-K+-ATP酶相互作用。结果表明，AT 1 R和D1 R作为一个对立的单位，这应该提供一个高度通用和敏感的系统，短期调节钠排泄。
Sodium excretion is bidirectionally regulated by dopamine, acting on D1-like receptors (D1R) and angiotensin II, acting on AT(1) receptors (AT1R). Since sodium excretion has to be regulated with great precision within a short frame of time, we tested the short-term effects of agonist binding on the function of the reciprocal receptor within the D1R-AT1R complex in renal proximal tubule cells. Exposure of rat renal proximal tubule cells to a D1 agonist was found to result in a rapid partial internalization of AT1R and complete abolishment of AT1R signaling. Similarly, exposure of rat proximal tubule cells and renal tissue to angiotensin II resulted in a rapid partial internalization of D1R and abolishment of D1R signaling. D1R and AT1R were, by use of coimmunoprecipitation studies and glutathione-S-transferase pull-down assays, shown to be partners in a multiprotein complex. Na+-K+-ATPase, the target for both receptors, was included in this complex, and a region in the COOH-terminal tail of D1R (residues 397-416) was found to interact with both AT1R and Na+-K+-ATPase. Results indicate that AT1R and D1R function as a unit of opposites, which should provide a highly versatile and sensitive system for short-term regulation of sodium excretion.