多巴胺D_3受体激动剂对肾脏G蛋白亚基Gα_(12)、Gα_(13)与D_3受体耦联的影响  

Effect of D_3 Dopamine Receptor Agonist on the Renal D_3 Receptor/Gα_(12) and D_3 Recpetor/Gα_(13) Linkage

作　　者：杨剑[1] 于长青[1] 石伟彬[1] 傅春江[1] 何多芬[1] Laureano D. Asico Pedro A. Jose 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100012 [2]Department of Pediatrics, Georgetown University Medical Center,Washington,DC

出　　处：《中华高血压杂志》2008年第9期807-811,共5页Chinese Journal of Hypertension

基　　金：国家科技部973计划前期研究专项课题2008CB517308;国家自然科学基金30470728、30672199

摘　　要：目的观察多巴胺 D_3受体激动剂对肾脏 G 蛋白亚基 Gα_(12)和 Gα_(13)与 D_3受体耦联的影响。方法以WKY(Wistar-Kyoto)大鼠与自发性高血压大鼠(SHR)及其来源的肾脏皮质膜、肾脏刷状缘膜(BBM)以及近曲小管上皮细胞株(RPT)为研究对象,利用多巴胺 D_3受体激动剂 PD128907刺激 D_3受体,运用免疫共沉淀观察PD128907对 D_3受体与 Gα_(12)、Gα_(13)的相互关联的影响,并在 WKY 与 SHR 中对比关联改变与功能差异。结果 D_3/Gα_(12)与 D_3/Gα_(13)之间在 WKY 与 SHR 中均存在共连接。PD128907刺激 D_3受体后,在 WKY 中可明显增加 D_3/Gα_(12)以及 D_3/Gα_(13)之间的连接程度;在 SHR 中却显著降低 D_3/Gα_(12)以及 D_3/Gα_(13)之间的连接。其中,D_3/Gα_(13)在 SHR 中的基础连接程度明显强于 WKY,D_3/Gα_(12)连接基础状态在 WKY 与 SHR 之间无明显差异。采用 PD128907直接灌注 WKY 和 SHR 大鼠右肾动脉,发现 PD128907可以明显增强 WKY 的尿钠排泄率(FE_(Na)),但却对 SHR 的 FE_(Na)没有影响。结论 D_3受体激动剂可明显调节 D_3/Gα_(12)以及 D_3/Gα_(13)之间的连接程度,该调节作用异常可能在高血压的发生发展中发挥一定作用。Objective To investigate the effect of a D3 dopamine receptor agonist on the renal D3 receptor/Gα12 and D3, recpetor/Gα13 linkage. Methods The renal cortical membrane, brush border membrane and renal proximal tubule （RPT） cells from Wistar Kyoto （WKY） rats and spontaneously hypertensive rats （SHRs） were used in this experiment. The renal D3 receptor/Gα12 and D3 recpetor/Gα13 linkage were determined by co-immunoprecipitation witb or without D~ receptor agonist （PD128907） treatment. The differences of the above-mentioned parameters between WKY and SHRs were compared. Results There are co-immunoprecipitation between D3 receptor and Gα12 , D3 receptor and Gα13 in both WKY and SHR. PD128907 increased the linkage of D3/Gα13 or D3/Gα13 in renal cortical membrane, brush border membrane and renal proximal tubule （RPT） cells from WKY rats, in contrast, decreased it in SHRs. The basal levels of D3/Gα13 were higher in WKY rats than in SHRs. Infusion of PD128907, via right artery, increased sodium fractional rate in WKY rats, but not in SHRs. Conclusion Activation of D3 receptor up-regulates the linkage of D3/Gα13 or D3/Gα13 in WKY rats, the impaired regulation might be involved into the pathogenesis of essential hypertension.

关 键 词：多巴胺D3受体 Gα12 Gα13 肾脏 高血压 

分 类 号：R544.1[医药卫生—心血管疾病]