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目的探讨多巴胺D3受体对肾脏内皮素B(ETB)受体表达及功能的调节与高血压(EH)发生的关系。方法分别以D3多巴胺受体基因敲除(D3-/-)小鼠和肾脏近曲小管上皮细胞(RPT)株为研究对象,观察刺激D3受体后ETB受体蛋白表达和功能的变化,D3受体的蛋白表达采用免疫印迹测定,ETB受体的功能采用Na+-K+-ATP酶活性表示。结果D3-/-小鼠肾脏皮质ETB受体的蛋白表达(0·8±0·2)DU明显低于对照小鼠[(1·2±0·1)DU,P<0·05,n=5];D3受体兴奋剂PD128907(10-7mol/L·24h)刺激D3受体可增加Wistar-Kyoto(WKY)大鼠RPT细胞ETB受体的表达,却抑制自发性高血压(SHR)大鼠ETB受体的表达[WKY(对照1·0±0·1比PD1289071·5±0·1)DU;SHR(对照1·0±0·1比PD1289070·7±0·2)DU;n=9,P<0·05]。用ETB受体激动剂BQ3020(10-8mol/L·15min)刺激ETB受体可明显降低WKY大鼠RPT细胞的Na+-K+-ATP酶的活性,但在SHR的RPT细胞,这种抑制作用却丧失;基础状态下SHR的Na+-K+-ATP酶活性明显高于WKY大鼠。预先刺激D3受体均可使ETB受体对Na+-K+-ATP酶活性的抑制作用进一步加强,但这种作用在WKY的RPT细胞明显强于SHR的RPT细胞(下降幅度SHR9·1%比WKY16·9%)。结论D3受体通过对ETB受体蛋白表达的调节作用,从而调控ETB受体的功能,D3/ETB受体之间的异常调节参与了EH发生的发病机制。
Objective To investigate the relationship between the expression of dopamine D3 receptor on renal endothelin B (ETB) receptor and its function and the occurrence of hypertension (EH). Methods The expression of ETB receptor protein and function in D3 dopamine receptor knockout (D3 - / -) mice and renal proximal tubule epithelial cells (RPT) were studied respectively. D3 The protein expression of the receptor was measured by immunoblotting and the function of the ETB receptor was expressed as Na + -K + -ATPase activity. Results The protein expression of ETB receptor in renal cortex of D3 - / - mice (0.8 ± 0.2) DU was significantly lower than that of the control mice [(1.2 ± 0.1) DU, P <0.05 · n = 5]. D3 receptor agonist PD128907 (10-7mol / L · 24h) stimulated the expression of ETB receptor in RPT cells of Wistar-Kyoto (WKY) rats but inhibited SHR Rat ETB receptor expression [WKY (control 1.0 ± 0.1 vs. PD1289071.5 ± 0.1) DU; SHR (control 1.0 ± 0.1 · PD1289070 · 7 ± 0.2) DU; n = 9, P <0 · 05]. Stimulation of ETB receptors with ETQ receptor agonist BQ3020 (10-8 mol / L · 15 min) significantly reduced the activity of Na + -K + -ATPase in RPT cells of WKY rats, but in RPE cells of SHR, the inhibitory effect was Loss; basic state SHR Na + -K + -ATP enzyme activity was significantly higher than WKY rats. Pretreatment with D3 receptor further potentiated the inhibitory effect of ETB receptors on Na + -K + -ATPase activity, but this effect was stronger in RP-1 cells of WKY than that of SHR-RPT cells (SHR9.1% vs WKY16 ·9%). Conclusion The D3 receptor regulates the function of ETB receptor by regulating the expression of ETB receptor protein. The abnormal regulation of D3 / ETB receptors is involved in the pathogenesis of EH.