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目的研究多巴胺D4受体对肾脏近曲小管(RPT)上皮细胞Na+-K+-ATP酶活性的影响及其机制。方法以WKY大鼠的RPT细胞株作为研究对象,测定多巴胺D4受体激动剂PD168077对RPT细胞Na+-K+-ATP酶活性的影响,硝酸还原酶法检测一氧化氮含量。结果PD168077能明显降低RPT细胞Na+-K+-ATP酶的活性,该作用呈浓度和时间依赖性。多巴胺D4受体拮抗剂L745870(10-6mol/L)可阻断PD168077对RPT细胞Na+-K+-ATP酶活性的抑制。与对照组比较,PD168077刺激RPT细胞15 min后,一氧化氮的合成含量明显升高;一氧化氮合成酶抑制剂可以阻断多巴胺D4受体对Na+-K+-ATP酶的抑制效应,提示一氧化氮途径可能参与了多巴胺D4受体对RPT细胞Na+-K+-ATP酶的抑制作用。结论多巴胺D4受体能够抑制WKY大鼠RPT细胞Na+-K+-ATP酶的活性,该作用可能与一氧化氮途径有关。
Objective To investigate the effect of dopamine D4 receptor on Na + -K + -ATPase activity in renal proximal tubule (RPT) epithelial cells and its mechanism. Methods The RPT cell line of WKY rats was used as the research object to determine the effect of dopamine D4 receptor agonist PD168077 on the activity of Na + -K + -ATPase in RPT cells. Nitric acid reductase method was used to detect the content of nitric oxide. Results PD168077 could significantly reduce the activity of Na + -K + -ATPase in RPT cells in a concentration- and time-dependent manner. Dopamine D4 receptor antagonist L745870 (10-6mol / L) can block PD168077 RPT cell Na + -K + -ATPase inhibition. Compared with the control group, PD168077 stimulated RPT cells for 15 min, the synthesis of nitric oxide significantly increased; nitric oxide synthase inhibitors can block dopamine D4 receptor Na + -K + -ATPase inhibition, suggesting that a Nitric oxide pathway may be involved in the inhibition of dopamine D4 receptor on RPT cells Na + -K + -ATPase. Conclusion Dopamine D4 receptor can inhibit the activity of Na + -K + -ATPase in RPT cells in WKY rats, which may be related to the nitric oxide pathway.