Dopamine enhances duodenal epithelial permeability via the dopamine D5 receptor in rodent
Dopamine enhances duodenal epithelial permeability via the dopamine D5 receptor in rodent
复制标题
多巴胺通过多巴胺 D5 受体增强啮齿动物十二指肠上皮的通透性。
DOI：
10.1111/apha.12806
复制
发表时间：
2017-05-01
影响因子：
6.3
通讯作者：
Zhu, J. -X.
中科院分区：
文献类型：
--
作者：
Feng, X. -Y.;Zhang, D. -N.;Zhu, J. -X.
目的肠屏障由上皮细胞和细胞间连接复合物组成，调节上皮细胞离子转运和通透性。多巴胺（Dopamine，DA）可通过D1样受体（D1-like receptor，D1 R）和D5样受体（D5 R）促进十二指肠上皮细胞离子转运，但D1样受体是否影响十二指肠通透性尚不清楚。结果多巴胺可使人D5 R转基因小鼠和高内源性肠DA（HEnD）大鼠的I-SC向下偏转，并可使人D5 R转基因小鼠和高内源性肠DA大鼠的FITC-D1样受体拮抗剂SCH-23390可抑制对照大鼠十二指肠的葡聚糖通透性。然而，DA降低了十二指肠跨上皮电阻（TER），SCH-23390也逆转了该效应。在对照大鼠的十二指肠中观察到D5 R的强免疫荧光信号，而不是D1 R。在人D5 R基因敲入转基因小鼠中，十二指肠粘膜显示基础I-SC增加，具有高FITC-葡聚糖渗透性，TER降低，紧密连接蛋白表达降低，表明这些转基因小鼠的十二指肠屏障功能减弱。D5 R敲低转基因小鼠表现出降低的基础I-SC，降低FITC-葡聚糖渗透性。此外，增加FITC-葡聚糖通透性结合降低TER和紧密连接蛋白的表达在十二指肠粘膜也观察到在HEnD rats.ConclusionThis研究表明，第一次，DA通过D5 R增加对照大鼠的十二指肠通透性，这为DA对十二指肠上皮屏障功能的影响提供了新的实验和理论证据。
AimThe intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D-1 (D1R) and D-5 (D5R), but whether D1-like receptors influence the duodenal permeability is unclear.MethodsFITC-dextran permeability, short-circuit current (I-SC), Western blot, immunohistochemistry and ELISA were used in human D5R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study.ResultsDopamine induced a downward deflection in I-SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D5R, but not D1R, was observed in the duodenum of control rat. In human D5R knock-in transgenic mice, duodenal mucosa displayed an increased basal I-SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D5R knock-down transgenic mice manifested a decreased basal I-SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats.ConclusionThis study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D5R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function.