Renal D3 dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions
Renal D3 dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions
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DOI：
10.1038/ki.2008.247
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发表时间：
2008-09-01
影响因子：
19.6
通讯作者：
Jose, Pedro A.
中科院分区：
文献类型：
--
作者：
Zeng, Chunyu;Asico, Laureano D.;Jose, Pedro A.
多巴胺能和内皮素系统通过调节肾近端小管中的钠转运参与控制血压。在小鼠中，内皮素B受体（ET B）或D（3）多巴胺受体基因的破坏都会产生高血压。为了检查这两种受体是否相互作用，我们通过选择性地将试剂输注到麻醉大鼠的右肾中来研究Wistar-Kyoto（WKY）和自发性高血压（SHR）大鼠。D（3）受体激动剂（PD 128907）引起WKY大鼠尿钠排泄，ETB受体拮抗剂部分阻断了这种作用。相比之下，PD 128907在SHR中减弱钠排泄。激光共聚焦显微镜观察发现对照组WKY细胞ETB受体主要定位于细胞膜。用D（3）受体拮抗剂处理导致其内化到含有D（3）受体的细胞内区室中。联合应用D（3）和ETB拮抗剂不能使WKY大鼠细胞中的ETB受体内化。与此相反，在SHR细胞中，ETB受体在基础条件下主要存在于内部隔室中，因此可能被阻止与激动剂刺激的膜结合D（3）受体相互作用。我们的研究表明，D（3）受体与近端小管ETB受体物理相互作用，多巴胺在SHR中的利钠作用减弱可能部分由异常的D（3）/ETB受体相互作用解释。
Dopaminergic and endothelin systems participate in the control blood pressure by regulating sodium transport in the renal proximal tubule. Disruption of either the endothelin B receptor (ETB) or D(3) dopamine receptor gene in mice produces hypertension. To examine whether these two receptors interact we studied the Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats by selectively infusing reagents into the right kidney of anesthetized rats. The D(3) receptor agonist (PD128907) caused natriuresis in WKY rats which was partially blocked by the ETB receptor antagonist. In contrast, PD128907 blunted sodium excretion in the SHRs. We found using laser confocal microscopy that the ETB receptor was mainly located in the cell membrane in control WKY cells. Treatment with the D(3) receptor antagonist caused its internalization into intracellular compartments that contained the D(3) receptors. Combined use of D(3) and ETB antagonists failed to internalize ETB receptors in cells from WKY rats. In contrast in SHR cells, ETB receptors were found mainly in internal compartments under basal condition and thus were likely prevented from interacting with the agonist-stimulated, membrane-bound D(3) receptors. Our studies suggest that D(3) receptors physically interact with proximal tubule ETB receptors and that the blunted natriuretic effect of dopamine in SHRs may be explained, in part, by abnormal D(3)/ETB receptor interactions.