Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats

American Journal of Physiology. Cell Physiology
Michelle T BaratiSyed Jalal Khundmiri

Abstract

Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosph...Continue Reading

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Citations

May 23, 2018·Clinical and Experimental Hypertension : CHE·Jianling LiWeifeng Wu
Aug 15, 2019·American Journal of Physiology. Renal Physiology·Anees A BandayMustafa Lokhandwala
Jan 28, 2020·American Journal of Physiology. Renal Physiology·Adrienne M Bushau-Sprinkle, Eleanor D Lederer
Mar 31, 2019·The American Journal of Pathology·Adrienne Bushau-SprinkleEleanor D Lederer

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Methods Mentioned

BETA
immunoprecipitation
transfection
confocal microscopy

Software Mentioned

Proteome
Sequest
Scaffold
Xcalibur
Proteome Discoverer
Scaffold Q + S
SequestHT
GraphPad Prism
Mascot

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