Journal article
自发性高血压大鼠发育过程中D1多巴胺受体对钠-氢交换体3的调节
中华医学杂志, Vol.81(9), pp.549-552
05/10/2001
DOI: 10.3760/j:issn:0376-2491.2001.09.011
PMID: 11809121
Abstract
Objective: To determine if spontaneous hypertension is secondary to defective interaction among dopamine receptor, G protein, and Na(+)/H(+) exchanger 3 (NHE3).
Methods: The inhibitory effect of a D(1) dopamine agonist upon NHE3 activity and its impact upon G(s)alpha/NHE3 binding in renal brush border membrane (BBM) of spontaneously hypertensive rats (SHRs) 2 - 3 weeks before and 12 weeks after the establishment of hypertension were examined. In order to avoid the confounding influence of second messenger on D(1) receptor/NHE3 interaction, study was made in BBM devoid of cytoplasmic component.
Results: NHE3 activity increased with age in Wister-Kyoto (WKY) rats but not in SHRS. D1 receptor expression did change with age in both WKY rats and SHRs. The inhibitory effect of a D(1)-like agonist on NHE3 activity increased with age in WKY rats but not in SHRs. In WKY rats, another D(1)-like agonist, fedoldopam, increased G(s)alpha/NHE3 binding to the same extent in 2 week old and adult rats, but decreased the amount of G(s)(alpha)bound to NHE3 in 2 week old SHRs.
Conclusion: The decrease of inhibitory effect of D(1)-like agonist upon NHE3 activity in SHRs precedes the development of hypertension. Spontaneous hypertension may be caused, in part, by a decreased interaction between G(s)alpha and NHE3 in BBM secondary to D(1)-like receptor function.
R544; 目的探讨是否原发性高血压继发于多巴胺受体、G蛋白和Na+-H+交换体-3(NHF3)的相互作用障碍.方法为避免第二信使的影响,我们采用无细胞质成分的肾小管细胞膜刷状缘进行实验,实验对象为高血压产生前(2～3周龄)和高血压产生后(12周龄)的自发性高血压大鼠(SHR),研究多巴胺受体激活剂对SHR肾小管细胞膜刷状缘的NHE活性的抑制作用和对G蛋白亚基与NHF3结合的影响.结果正常对照鼠(WKY鼠)NHE3活性随年龄增长而增强,但SHR肾NHE3活性未随年龄变化而改变.SHR与WKY鼠的D1多巴胺受体表达不受年龄影响.多巴胺D1受体激活剂对WKY肾NHE3活性的抑制能力随年龄增长而增强,但对SHR的抑制未随年龄变化.多巴胺D1受体激活剂(Fenoldopam)增加WKY幼鼠Gsa/NHE3结合量与成年鼠相同,但使SHR幼鼠Gsa/NHE3结合量减少.结论多巴胺D1受体激活剂对SHR中NHE3活性的抑制减少早于高血压的形成,可能D1受体功能损害导致的Gsa蛋白与NHE3相互作用减少在高血压的形成发挥了部分作用.
Details
- Title: Subtitle
- 自发性高血压大鼠发育过程中D1多巴胺受体对钠-氢交换体3的调节
- Creators
- 李晓曦Frederick E Albrecht - Georgetown University Medical Center徐镜Jean E RobillardGilbert M EisnerPedro A Jose
- Resource Type
- Journal article
- Publication Details
- 中华医学杂志, Vol.81(9), pp.549-552
- Publisher
- 中山医科大学附属第一医院外科 广州,%Georgetown University Medical Center, Washington, DC, USA%Universityof Michigan Medical Center, Ann Arbor, MI, USA
- DOI
- 10.3760/j:issn:0376-2491.2001.09.011
- PMID
- 11809121
- ISSN
- 0376-2491
- Grant note
- 美国国立卫生研究所项目; Regulation of NHE3 by D1 dopamine receptor during development of spontaneously hypertensive rats ((DK39308); (DK44756,HL23081,HL58536))
- Alternative title
- Regulation of NHE3 by D1 dopamine receptor during development of spontaneously hypertensive rats
- Language
- Chinese
- Date published
- 05/10/2001
- Academic Unit
- Molecular Physiology and Biophysics; Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Medicine Administration
- Record Identifier
- 9984774209302771
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