多巴胺D_3受体对SHR大鼠肾脏内皮素B受体的异常调节在高血压发生中的作用  

Role of D_3 Dopamine Receptor Regulation of ETB receptor in Renal Proximal Tubule Cells in Essential Hypertension

作　　者：刘琰[1,2] 曾春雨[1] 何多芬[1] 崔志刚[1] 石伟彬[1] 李震[1] 杨剑[1] 黄河飞[1] 张晔[1] 杨成明[1] 王旭开[1] 周林[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 [2]河南省郑州市解放军第153医院老年病科,河南郑州450042

出　　处：《中华高血压杂志》2006年第12期965-969,共5页Chinese Journal of Hypertension

基　　金：国家自然基金资助项目(30470728;30672199)

摘　　要：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 determine the relationship between hypertension and the regulation of D3 dopamine receptor on ETB receptor in kidney. Methods D3 receptor null （D3-/-） mice and immortalized renal proximal tubule （RPT） cells were used in this study. ETB receptor protein expression was determined by Western blot. ETB receptor function was investigated by measurement of Na^＋-K^＋-ATPase activity. Results ETB receptor protein expression was lower in renal cortex of D3-/- mice than in control mice（0. 8± 0. 2 vs control：1. 2± 0.1 density units, DU, P〈0. 05, n= 5 ）. Activation of D3 receptor in RPT cells in Wistar-Kyoto（WKY） rats by D3 receptor agonist PD128907 1-10-7 mol/（ L · 24 h）] increased ETB receptor expression. On contrary, PD128907 decreased ETB receptor expression in RPT cells in SHR（WKY： 1.0±0. 1 vs 1.5±0. 1 DU;SHR： 1.0 ± 0. 1 vs 0. 7 ：]： 0. 2 DU ; n = 9, P〈 0. 05 ）. Stimulation of ETB receptor with selective ETB receptor agonist, BQ3020 （10-Smol/L · 15min）, decreased Na^＋-K^＋-ATPase activity in WKY ceils. However, the inhibitory effect of ETB receptor on Na^＋-K^＋ - ATPase activity was lost in SHR cells. The basal level of Na^＋-K^＋-AT- Pase activity was higher in SHR cells as compared with WKY cells. The inhibitory effect of ETB receptor on Na^＋-K^＋-ATPase activity was augmented by pretreatment with D3 receptor agonist 1-PD128907, 10-7 mol/（L· 24 h）]in both WKY and SHR cells, while the augmented effect was higher in WKY cells （SHR： 9.1% vs WKY： 16.9%）. Conclusion Activation of D3 receptor could regulate ETB receptor function by upregulation of ETB re ceptor protein expression. The D3/ETB receptor interaction may be involved in the pathophysiology of essential hypertension.

关 键 词：D3受体 ETB受体 肾脏近曲小管上皮细胞 Na^+ -K^+ -ATP酶 聩多巴胺受体基因敲除小鼠 

分 类 号：R544.1[医药卫生—心血管疾病]