ArticlePflugers Archiv : European journal of physiology2009
Defective jejunal and colonic salt absorption and alteredNa(+)/H (+) exchanger 3 (NHE3) activity in NHE regulatory factor 1 (NHERF1) adaptor protein-deficient mice.
Article in Pflugers Archiv : European journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
- Pharmacodynamics, Safety, and Tolerability of the NHE3 Inhibitor Tenapanor: Two Trials in Healthy Volunteers.Clinical drug investigation · 2018Trial
- A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers.Clinical and experimental nephrology · 2017Trial
- Review
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Physiologically Based Biopharmaceutics Model (PBBM) of Minimally Absorbed Locally Acting Drugs in the Gastrointestinal Tract-Case Study: Tenapanor.Pharmaceutics · 2023Article
- Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal NaHypertension (Dallas, Tex. : 1979) · 2022Article
- ERM-1 Phosphorylation and NRFL-1 Redundantly Control Lumen Formation in theFrontiers in cell and developmental biology · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- NaJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- A Critical Role for NaJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut: A new antihypertensive concept.International journal of cardiology. Heart & vasculature · 2020Review
- Impairment of electroneutral NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2020Article
- NHERF3 is necessary forAmerican journal of physiology. Cell physiology · 2019Article
- The role of splanchnic congestion and the intestinal microenvironment in the pathogenesis of advanced heart failure.Current opinion in supportive and palliative care · 2019Review
- Urinary concentrating defect in mice lacking Epac1 or Epac2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Visceral Congestion in Heart Failure: Right Ventricular Dysfunction, Splanchnic Hemodynamics, and the Intestinal Microenvironment.Current heart failure reports · 2017Review
- Effects of Tenapanor on Cytochrome P450-Mediated Drug-Drug Interactions.Clinical pharmacology in drug development · 2017Article
- Preclinical and Healthy Volunteer Studies of Potential Drug-Drug Interactions Between Tenapanor and Phosphate Binders.Clinical pharmacology in drug development · 2017Article
- Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance.Oncogene · 2017Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
We investigated the role of the Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) on intestinal salt and water absorption, brush border membrane (BBM) morphology, and on the NHE3 mRNA expression, protein abundance, and transport activity in the murine intestine. NHERF1-deficient mice displayed reduced jejunal fluid absorption in vivo, as well as an attenuated in vitro Na(+) absorption in isolated jejunal and colonic, but not of ileal, mucosa. However, cAMP-mediated inhibition of both parameters remained intact. Acid-activated NHE3 transport rate was reduced in surface colonocytes, while its inhibition by cAMP and cGMP was normal. Immunodetection of NHE3 revealed normal NHE3 localization in the BBM of NHERF1 null mice, but NHE3 abundance, as measured by Western blot, was significantly reduced in isolated BBM from the small and large intestines. Furthermore, the microvilli in the proximal colon, but not in the small intestine, were significantly shorter in NHERF1 null mice. Additional knockout of PDZK1 (NHERF3), another member of the NHERF family of adaptor proteins, which binds to both NHE3 and NHERF1, further reduced basal NHE3 activity and caused complete loss of cAMP-mediated NHE3 inhibition. An activator of the exchange protein activated by cAMP (EPAC) had no effect on jejunal fluid absorption in vivo, but slightly inhibited NHE3 activity in surface colonocytes in vitro. In conclusion, NHERF1 has segment-specific effects on intestinal salt absorption, NHE3 transport rates, and NHE3 membrane abundance without affecting mRNA levels. However, unlike PDZK1, NHERF1 is not required for NHE3 regulation by cyclic nucleotides.
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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 OpenQuestion graph.