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目的研究多巴胺D4受体对肾脏近曲小管上皮(RPT)细胞胰岛素受体表达和功能的影响。方法以RPT细胞株为研究对象,采用免疫印迹法测定D4受体激动剂PD168077刺激D4受体后胰岛素受体的表达变化,并探讨其作用机制。结果D4受体激动剂PD168077(10-7mol/L,24 h)可明显抑制WKY大鼠RPT细胞胰岛素受体的表达,该作用呈现浓度和时间依赖性关系。PD168077对胰岛素受体表达的抑制作用可被D4受体特异性拮抗剂L745870(10-6mol/L)所阻断。与单用胰岛素相比,在PD168077(10-7mol/L,24 h)预先刺激的情况下,胰岛素对Na+-K+-ATP酶活性的刺激作用降低了39%(P<0.05)。钙离子通道阻断剂尼卡地平(10-7mol/L)可以阻断PD168077对RPT细胞胰岛素受体的抑制作用。结论D4受体对胰岛素受体蛋白表达和功能具有抑制作用,此作用可能通过钙离子通道发挥影响。
Objective To investigate the effect of dopamine D4 receptor on insulin receptor expression and function in renal proximal tubule epithelial (RPT) cells. Methods The RPT cell line was used as the research object. The expression of insulin receptor was detected by immunoblotting after D4 receptor agonist PD168077 stimulated D4 receptor and its mechanism of action was investigated. Results D4 receptor agonist PD168077 (10-7mol / L, 24 h) significantly inhibited insulin receptor expression in RPT cells in WKY rats in a time-and concentration-dependent manner. The inhibitory effect of PD168077 on insulin receptor expression can be blocked by D4 receptor specific antagonist L745870 (10-6mol / L). Stimulation of insulin on Na + -K + -ATPase activity was reduced by 39% (P <0.05) in the presence of PD168077 (10-7 mol / L, 24 h) prior to stimulation with insulin alone. Nicardipine (10-7mol / L), a calcium channel blocker, can block the inhibitory effect of PD168077 on insulin receptor of RPT cells. Conclusion D4 receptor has an inhibitory effect on the expression and function of insulin receptor protein, and this effect may play an important role through calcium channel.