多巴胺D3受体对肾脏近曲小管上皮细胞D5受体的影响在高血压发生中的作用  

D_3 Dopamine Receptor Augmentation of D_5 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells

作　　者：黄河飞[1] 何多芬[1] 石伟彬[1] 于长青[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9期802-806,共5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：目的观察多巴胺 D_3受体对肾脏近曲小管(RPT)上皮细胞上多巴胺 D_3受体表达和功能的影响。方法以 Wistar-Kyoto(WKY)大鼠与自发性高血压大鼠(SHR)为研究对象,利用免疫印迹法观察 D_3受体对 D_5受体蛋白表达的影响;并采用 Na^+-K^+-ATP 酶活性测定方法在转染 D_5受体的人胚肾293细胞(HEK293-D_5)上观察D_3受体对 D_5受体影响的病理生理学意义。结果刺激 D_3受体可增强 D_5受体的蛋白表达,该作用呈浓度和时间依赖性;同时能被 D_3受体特异性阻断剂所阻断;在高血压状态下,这种作用受损。刺激 D_5受体可抑制 Na^+-K^+-ATP 酶的活性,在预先刺激 D_3受体的情况下可使 D_5受体对 Na^+-K^+-ATP 酶活性的抑制作用进一步增强。结论D_3受体对肾脏近曲小管上皮细胞上 D_5受体的表达和功能具有促进作用,这种作用的受损可能在原发性高血压的发生发展中具有一定影响。Objective To investigate the effect of D3 dopamine receptor on D5 dopamine receptor in rat renal proximal tubule （RPT） cells. Methods The RPT cells from Wistar-Kyoto（WKY） rats and spontaneously hypertensive rats （SHRs） were used in this study, the receptor expression was determined by immunoblotting, the activity of Na^＋-K^＋-ATPase was determined by Na^＋-K^＋-ATPase assay experiment in D5 receptor transfected HEN293 cells. Results The D3 receptor agonist PD128907 increased the expression of D5 receptors in a concentration and time- dependent manner; these effects were blocked by the D3 receptor antagonist U99194A. In the SHR cells, the up-regulation of D3 receptor on D5 receptor was impaired. Pretreatment with I）3 receptor agonist augmented the in- hibitory effect of Ds receptor on Na^＋-K^＋ ATPase activity in D5 receptor transfected HEK293 cells. Conclusion The impaired upregulation of D3 receptor on D5 receptor in RPT cells might be involved into the pathogenesis of essential hypertension.

关 键 词：多巴胺受体 肾脏近曲小管上皮细胞 高血压 肾脏 

分 类 号：R544.1[医药卫生—心血管疾病]