# Dopaminergic and angiotensin regulation of sodium metabolism via the sodium bicarbonate co-transporter (SLC4A5) in the human renal proximal and distal tubule cells: Role of GRK4 on salt sensitivity

> **NIH NIH P01** · UNIVERSITY OF VIRGINIA · 2020 · $396,706

## Abstract

ABSTRACT FOR PROJECT 1
The goal of this research proposal is to extend our studies of how the renin angiotensin system
(RAS) and dopaminergic systems regulate renal sodium transport and ultimately their
involvement in the etiology of salt sensitivity (a pathology affecting 51% of hypertensive and
26% of normotensive individuals). Specifically, we will test the overall hypothesis that the
electrogenic sodium bicarbonate cotransporters NBCe2 (coded by the gene SLC4A5) and
NBCe1 (coded by the gene SLC4A4) are involved with sodium homeostasis through regulation
by the RAS and dopaminergic systems and other critical sodium transporters (NHE3 and
Na+,K+/ATPase). Furthermore, two single nucleotide polymorphisms (SNPs) in SLC4A5 lead to
the dysregulation of sodium reabsorption through increases in SLC4A5 mRNA expression and
NBCe2 activity. The specific aims for this project are: (1) To test the hypothesis that salt
sensitivity is due to aberrant dopaminergic and angiotensin regulation of renal proximal tubule
sodium transport caused by intronic variants in SLC4A5 and a variant of GRK4 (GRK4-65L) and
(2) To test the hypothesis in specific aim 1 by investigating the epigenetic regulation of the
expression of NBCe2 (and related ion transporters) by an HNF4A binding site in the SLC4A5
gene.

## Key facts

- **NIH application ID:** 9949770
- **Project number:** 5P01HL074940-15
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Robin A Felder
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,706
- **Award type:** 5
- **Project period:** — → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949770

## Citation

> US National Institutes of Health, RePORTER application 9949770, Dopaminergic and angiotensin regulation of sodium metabolism via the sodium bicarbonate co-transporter (SLC4A5) in the human renal proximal and distal tubule cells: Role of GRK4 on salt sensitivity (5P01HL074940-15). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9949770. Licensed CC0.

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