内皮素B受体对自发性高血压大鼠肾脏近曲小管上皮细胞多巴胺D3受体的异常调节  

Regulation of ETB Receptor on D3 Dopamine Receptor in Renal Proximal Tubule Cells from Spontaneously Hypertensive Rats

作　　者：石伟彬[1] 于长青[1] 杨剑[1] 何多芬[1] 傅春江[1] 杨成明[1] 王旭开[1] 黄岚[2] 周林[1] 曾春雨[1] 

机构地区：[1]第三军医大学大坪医院(野战外科研究所)心内科心血管病研究室,重庆400042 [2]第三军医大学新桥医院心内科,重庆400037

出　　处：《中华高血压杂志》2008年第7期617-620,共4页Chinese Journal of Hypertension

基　　金：国家自然基金资助项目(30470728、30672199);国家科技部973前期项目(2008CB517308)

摘　　要：目的探讨内皮素 B(ETB)受体对肾脏近曲小管上皮细胞多巴胺 D_3受体表达的影响,以及其与高血压(EH)发生之间的关系。方法以 Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)肾脏近曲小管上皮细胞(RPT)株为研究对象,观察刺激 ETB 受体后 D_3受体蛋白表达的变化,D_3受体的蛋白表达采用免疫印迹测定,ETB/D_3受体之间的连接采用免疫沉淀测定。结果 ETB 受体激动剂 BQ3020可增加 WKY 大鼠 RPT 细胞 D_3受体的蛋白表达,该作用呈现出时间依赖性和剂量依赖性关系,而且 BQ3020对 D_3受体蛋白表达的刺激作用可以被D_3受体拮抗剂 BQ788所抑制。在 SHR 细胞,ETB 受体激动剂 BQ3020并不能增加 RPT 细胞 D_3受体的蛋白表达,并且基础状态下 D_3受体的蛋白表达在 SHR 细胞明显低于 WKY 细胞。免疫共沉淀显示在 ETB/D_3受体之间存在同连接,刺激 ETB 受体可增加 ETB/D_3受体之间的连接程度,然而,在 SHR 细胞,不仅基础状态下 ETB/D_3受体之间的连接程度低,而且,刺激 ETB 受体对 ETB/D_3受体之间的连接程度无影响。结论 ETB 受体具有对 D_3受体蛋白表达的调节作用,ETB/D_3受体之间的异常调节可能参与了 EH 发生的发病机制。Objective To determine the effect of ETB endothelin receptor on D3 dopamine receptor expression in renal proximal tubule （RPT） cells, and its relationship with hypertension. Methods The RPT cells from Wist- ar-Kyoto （WKY） rats and spontaneously hypertensive rats （SHRs） were used in this study. D3 receptor protein expression was determined by immunoblotting with or without ETB receptor stimulation. The linkage between ETB and Ds receptors was determined by immunoprecipitation. Results In WKY RPT cells, an ETB receptor agonist, BQ3020, increased D3 receptor protein in a time and concentration-dependent manner. The stimulatory effect of BQ3020 on Ds receptor protein was blocked by an ETB receptor antagonist （BQ788）. However, BQ3020 had no effect on D3 receptor expression in SHR cells. Moreover, basal D3 receptor protein expression was lower in SHR cells than in WKY cells. ETB/D3 receptors coimmunoprecipitated in RPT cells. Stimulation of ETB receptor increased ETB/D3 receptor coimmunoprecipitation in WKY cells, not in SHR cells, and the basal levels of ETB/D3 receptor coimmunoprecipitation was lower in SHR cells than in WKY cells. Conclusion ETB receptor regulates D3 receptor protein expression in RPT cells. An impaired ETB receptor regulation of the D3 receptor may participate in the pathogenesis of essential hypertension.

关 键 词：D3受体 内皮素B受体 肾脏近曲小管上皮细胞 高血压 

分 类 号：R544.1[医药卫生—心血管疾病]