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Kidney dopamine D1-like receptors and angiotensin 1-7 interaction inhibits renal Na+ transporters.

ABSTRACT: The role of dopamine D1-like receptors (DR) in the regulation of renal Na+ transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1-7 (ANG 1-7)-Mas receptor in the regulation of Na+ balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1-7 can regulate Na+ homeostasis by modulating the renal dopamine system. Sprague-Dawley rats were infused with saline alone (vehicle) or saline with ANG 1-7, ANG 1-7 antagonist A-779, DR agonist SKF38393, and antagonist SCH23390. Infusion of ANG 1-7 caused significant natriuresis and diuresis compared with saline alone. Both natriuresis and diuresis were blocked by A-779 and SCH23390. SKF38393 caused a significant, SCH23390-sensitive natriuresis and diuresis, and A-779 had no effect on the SKF38393 response. Concomitant infusion of ANG 1-7 and SKF38393 did not show a cumulative effect compared with either agonist alone. Treatment of renal proximal tubules with ANG 1-7 or SKF38393 caused a significant decrease in Na+-K+-ATPase and Na+/H+ exchanger isoform 3 activity. While SCH23390 blocked both ANG 1-7- and SKF38393-induced inhibition, the DR response was not sensitive to A-779. Additionally, ANG 1-7 activated PKG, enhanced tyrosine hydroxylase activity via Ser40 phosphorylation, and increased renal dopamine production. These data suggest that ANG 1-7, via PKG, enhances tyrosine hydroxylase activity, which increases renal dopamine production and activation of DR and subsequent natriuresis. This study provides evidence for a unidirectional functional interaction between two G protein-coupled receptors to regulate renal Na+ transporters and induce natriuresis.

SUBMITTER: Banday AA

PROVIDER: S-EPMC6843046 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Kidney dopamine D1-like receptors and angiotensin 1-7 interaction inhibits renal Na+ transporters.

Banday Anees A AA Diaz Andrea Diaz AD Lokhandwala Mustafa M

American journal of physiology. Renal physiology 20190814 4

The role of dopamine D1-like receptors (DR) in the regulation of renal Na+ transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1-7 (ANG 1-7)-Mas receptor in the regulation of Na+ balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1-7 can regulate Na+ homeostasis by modulating the renal dopamine system. Sprague-Dawley rats were infused with sa ...[more]

PMID: 31411069

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Project description:BackgroundTo control the osmotic pressure in the body, physiological adjustments to salinity fluctuations require the fish to regulate body fluid homeostasis in relation to environmental change via osmoregulation. Previous studies related to osmoregulation were focused primarily on the gill; however, little is known about another organ involved in osmoregulation, the kidney. The salinity adaptation of marine fish involves complex physiological traits, metabolic pathways and molecular and gene networks in osmoregulatory organs. To further explore of the salinity adaptation of marine fish with regard to the role of the kidney, the euryhaline fish Scatophagus argus was employed in the present study. Renal expression profiles of S. argus at different salinity levels were characterized using RNA-sequencing, and an integrated approach of combining molecular tools with physiological and biochemical techniques was utilized to reveal renal osmoregulatory mechanisms in vivo and in vitro.ResultsS. argus renal transcriptomes from the hyposaline stress (0‰, freshwater [FW]), hypersaline stress (50‰, hypersaline water [HW]) and control groups (25‰) were compared to elucidate potential osmoregulatory mechanisms. In total, 19,012 and 36,253 differentially expressed genes (DEGs) were obtained from the FW and HW groups, respectively. Based on the functional classification of DEGs, the renal dopamine system-induced Na+ transport was demonstrated to play a fundamental role in osmoregulation. In addition, for the first time in fish, many candidate genes associated with the dopamine system were identified. Furthermore, changes in environmental salinity affected renal dopamine release/reuptake by regulating the expression of genes related to dopamine reuptake (dat and nkaα1), vesicular traffic-mediated dopamine release (pink1, lrrk2, ace and apn), DAT phosphorylation (CaMKIIα and pkcβ) and internalization (akt1). The associated transcriptional regulation ensured appropriate extracellular dopamine abundance in the S. argus kidney, and fluctuations in extracellular dopamine produced a direct influence on Na+/K+-ATPase (NKA) expression and activity, which is associated with Na+ homeostasis.ConclusionsThese transcriptomic data provided insight into the molecular basis of renal osmoregulation in S. argus. Significantly, the results of this study revealed the mechanism of renal dopamine system-induced Na+ transport is essential in fish osmoregulation.

Dataset Information

Kidney dopamine D1-like receptors and angiotensin 1-7 interaction inhibits renal Na+ transporters.

Publications

Kidney dopamine D<sub>1</sub>-like receptors and angiotensin 1-7 interaction inhibits renal Na<sup>+</sup> transporters.

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