Acute regulation of renal Na+/H+ exchanger NHE3 by dopamine: role of protein phosphatase 2A

被引:23
作者
Bobulescu, I. Alexandru [1 ,4 ]
Quinones, Henry
Gisler, Serge M.
Di Sole, Francesca [4 ]
Hu, Ming-Chang [4 ]
Shi, Mingjun [4 ]
Zhang, Jianning
Fuster, Daniel G.
Wright, Nancy [2 ]
Mumby, Marc [2 ]
Moe, Orson W. [3 ,4 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Nephrol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA
[4] Univ Texas SW Med Ctr Dallas, Charles & Jane Pak Ctr Mineral Metab & Clin Res, Dallas, TX 75390 USA
关键词
natriuresis; sodium transport; signal transduction; K+-ATPASE ACTIVITY; SPONTANEOUSLY HYPERTENSIVE RATS; PROXIMAL TUBULE; SODIUM-EXCRETION; INTRARENAL DOPAMINE; VOLUME EXPANSION; BRUSH-BORDER; KINASE-A; DEPENDENT HYPERTENSION; NATRIURETIC RESPONSE;
D O I
10.1152/ajprenal.00708.2009
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Bobulescu IA, Qui ones H, Gisler SM, Di Sole F, Hu M, Shi M, Zhang J, Fuster DG, Wright N, Mumby M, Moe OW. Acute regulation of renal Na+/H+ exchanger NHE3 by dopamine: role of protein phosphatase 2A. Am J Physiol Renal Physiol 298: F1205-F1213, 2010. First published February 24, 2010; doi:10.1152/ajprenal.00708.2009.-Nephrogenic dopamine is a potent natriuretic paracrine/autocrine hormone that is central for mammalian sodium homeostasis. In the renal proximal tubule, dopamine induces natriuresis partly via inhibition of the sodium/proton exchanger NHE3. The signal transduction pathways and mechanisms by which dopamine inhibits NHE3 are complex and incompletely understood. This manuscript describes the role of the serine/threonine protein phosphatase 2A (PP2A) in the regulation of NHE3 by dopamine. The PP2A regulatory subunit B56 delta (coded by the Ppp2r5d gene) directly associates with more than one region of the carboxy-terminal hydrophilic putative cytoplasmic domain of NHE3 (NHE3-cyto), as demonstrated by yeast-two-hybrid, coimmunoprecipitation, blot overlay, and in vitro pull-down assays. Phosphorylated NHE3-cyto is a substrate for purified PP2A in an in vitro dephosphorylation reaction. In cultured renal cells, inhibition of PP2A by either okadaic acid or by overexpression of the simian virus 40 (SV40) small T antigen blocks the ability of dopamine to inhibit NHE3 activity and to reduce surface NHE3 protein. Dopamineinduced NHE3 redistribution is also blocked by okadaic acid ex vivo in rat kidney cortical slices. These studies demonstrate that PP2A is an integral and critical participant in the signal transduction pathway between dopamine receptor activation and NHE3 inhibition.
引用
收藏
页码:F1205 / F1213
页数:9
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