ArticleJCI insight2022
Epac1-/- and Epac2-/- mice exhibit deficient epithelial Na+ channel regulation and impaired urinary Na+ conservation.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Activation of GHSRs Facilitates the Excitability of Dentate Gyrus Granule Cells and Short-Term Spatial Memory via Multiple Ionic and Signaling Mechanisms.Advanced biology · 2026Article
- Epac2 Deficiency Compromises Adaptation to Dietary Acidification by Decreasing H+ Transport in the Renal Nephron.Function (Oxford, England) · 2025Article
- Intercalated Cell ClC-K2 Channel Contributes to Systemic ClFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Cyclic adenosine monophosphate critically modulates cardiac GLP-1 receptor's anti-inflammatory effects.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- TRPV4 expression in the renal tubule is necessary for maintaining whole body KAmerican journal of physiology. Renal physiology · 2023Article
- Blood pressure effects of sodium transport along the distal nephron.Kidney international · 2022Review
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Exchange proteins directly activated by cAMP (Epacs) are abundantly expressed in the renal tubules. We used genetic and pharmacological tools in combination with balance, electrophysiological, and biochemical approaches to examine the role of Epac1 and Epac2 in renal sodium handling. We demonstrate that Epac1-/- and Epac2-/- mice exhibit a delayed anti-natriuresis to dietary sodium restriction despite augmented aldosterone levels. This was associated with a significantly lower response to the epithelial Na+ channel (ENaC) blocker amiloride, reduced ENaC activity in split-opened collecting ducts, and defective posttranslational processing of α and γENaC subunits in the KO mice fed with a Na+-deficient diet. Concomitant deletion of both isoforms led to a marginally greater natriuresis but further increased aldosterone levels. Epac2 blocker ESI-05 and Epac1&2 blocker ESI-09 decreased ENaC activity in Epac WT mice kept on the Na+-deficient diet but not on the regular diet. ESI-09 injections led to natriuresis in Epac WT mice on the Na+-deficient diet, which was caused by ENaC inhibition. In summary, our results demonstrate similar but nonredundant actions of Epac1 and Epac2 in stimulation of ENaC activity during variations in dietary salt intake. We speculate that inhibition of Epac signaling could be instrumental in treatment of hypertensive states associated with ENaC overactivation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.