ArticleProceedings of the National Academy of Sciences of the United States of America2006
Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
- Epac2 Deficiency Compromises Adaptation to Dietary Acidification by Decreasing H+ Transport in the Renal Nephron.Function (Oxford, England) · 2025Article
- Histamine regulates the activity and the expression of the NaInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Divergence of Leptin Receptor and Interleukin-6 Receptor Subunit b in Early Vertebrate Evolution and Physiological Insights from the Sea Lamprey.Molecular biology and evolution · 2025Article
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Tissue Distribution, Expression and Regulation of Urea Transporters.Sub-cellular biochemistry · 2025Review
- A Review of Epithelial Ion Transporters and Their Roles in Equine Infectious Colitis.Veterinary sciences · 2024Review
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Inhibition of Transforming Growth Factor-β Improves Primary Renal Tubule Cell Differentiation in Long-Term Culture.Tissue engineering. Part A · 2023Article
- Epac induces ryanodine receptor-dependent intracellular and inter-organellar calcium mobilization in mpkCCD cells.Frontiers in physiology · 2023Article
- The organic cation transporter 2 regulates dopamine D1 receptor signaling at the Golgi apparatus.eLife · 2022Article
- The Interplay between Histamine HBiomolecules · 2021Article
- A peek into Epac physiology in the kidney.American journal of physiology. Renal physiology · 2019Article
- Urinary concentrating defect in mice lacking Epac1 or Epac2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- NaPi-IIa interacting partners and their (un)known functional roles.Pflugers Archiv : European journal of physiology · 2019Review
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Role of EPAC in cAMP-Mediated Actions in Adrenocortical Cells.Frontiers in endocrinology · 2016Review
- Review
- The G protein α subunit variant XLαs promotes inositol 1,4,5-trisphosphate signaling and mediates the renal actions of parathyroid hormone in vivo.Science signaling · 2015Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Na(+)/H(+) exchanger 3 (NHE3) is expressed in the brush border membrane (BBM) of proximal tubules (PT). Its activity is down-regulated on increases in intracellular cAMP levels. The aim of this study was to investigate the contribution of the protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC) dependent pathways in the regulation of NHE3 by adenosine 3',5'-cyclic monophosphate (cAMP). Opossum kidney cells and murine kidney slices were treated with cAMP analogs, which selectively activate either PKA or EPAC. Activation of either pathway resulted in an inhibition of NHE3 activity. The EPAC-induced effect was independent of PKA as indicated by the lack of activation of the kinase and the insensitivity to the PKA inhibitor H89. Both PKA and EPAC inhibited NHE3 activity without inducing changes in the expression of the transporter in BBM. Activation of PKA, but not of EPAC, led to an increase of NHE3 phosphorylation. In contrast, activation of PKA, but not of EPAC, inhibited renal type IIa Na(+)-coupled inorganic phosphate cotransporter (NaPi-IIa), another Na-dependent transporter expressed in proximal BBM. PKA, but not EPAC, induced the retrieval of NaPi-IIa from BBM. Our results suggest that EPAC activation may represent a previously unrecognized mechanism involved in the cAMP regulation of NHE3, whereas regulation of NaPi-IIa is mediated by PKA but not by EPAC.
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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 OpenQuestion graph.