ArticleThe Journal of clinical investigation2010
NHE4 is critical for the renal handling of ammonia in rodents.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 80 citations in OpenAlex.
- Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians.International journal of molecular sciences · 2026Review
- WDR72 Is Required for Urinary Acidification and Normal HActa physiologica (Oxford, England) · 2026Article
- Sex differences in renal acid-base regulation.American journal of physiology. Renal physiology · 2025Article
- Ammonia transport mediated by urea transporter A isoforms.Biology open · 2025Article
- Lack of a role of NHE4 in renal ammonia metabolism.American journal of physiology. Renal physiology · 2025Article
- State of knowledge on ammonia handling by the kidney.Pflugers Archiv : European journal of physiology · 2024Review
- Kidney metabolism and acid-base control: back to the basics.Pflugers Archiv : European journal of physiology · 2022Review
- A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives.Frontiers in immunology · 2022Review
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- The NaFrontiers in physiology · 2022Review
- Metabolic acidosis and hyperkalemia differentially regulate cation HCN3 channel in the rat nephron.Journal of molecular histology · 2020Article
- Multiple acid-base and electrolyte disturbances upregulate NBCn1, NBCn2, IRBIT and L-IRBIT in the mTAL.The Journal of physiology · 2020Article
- Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance.Seminars in nephrology · 2019Review
- p53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis.Nature · 2019Article
- Expression, Localization and Functional Activity of the Major Na⁺/H⁺ Exchange Isoforms Expressed in the Intestinal Cell Line Caco-2BBe.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2019Article
- Renal Tubular Acidosis: HAdvances in chronic kidney disease · 2018Review
- NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis.Scientific reports · 2018Article
- Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead.Pediatric health, medicine and therapeutics · 2018Review
- NHE1 has a notable role in metastasis and drug resistance of T-cell acute lymphoblastic leukemia.Oncology letters · 2017Article
- Evidence for ammonium conductance in a mouse thick ascending limb cell line.Physiological reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ammonia absorption by the medullary thick ascending limb of Henle's loop (MTALH) is thought to be a critical step in renal ammonia handling and excretion in urine, in which it is the main acid component. Basolateral Na+/H+ exchangers have been proposed to play a role in ammonia efflux out of MTALH cells, which express 2 exchanger isoforms: Na+/H+ exchanger 1 (NHE1) and NHE4. Here, we investigated the role of NHE4 in urinary acid excretion and found that NHE4-/- mice exhibited compensated hyperchloremic metabolic acidosis, together with inappropriate urinary net acid excretion. When challenged with a 7-day HCl load, NHE4-/- mice were unable to increase their urinary ammonium and net acid excretion and displayed reduced ammonium medulla content compared with wild-type littermates. Both pharmacologic inhibition and genetic disruption of NHE4 caused a marked decrease in ammonia absorption by the MTALH. Finally, dietary induction of metabolic acidosis increased NHE4 mRNA expression in mouse MTALH cells and enhanced renal NHE4 activity in rats, as measured by in vitro microperfusion of MTALH. We therefore conclude that ammonia absorption by the MTALH requires the presence of NHE4 and that lack of NHE4 reduces the ability of MTALH epithelial cells to create the cortico-papillary gradient of NH3/NH4+ needed to excrete an acid load, contributing to systemic metabolic acidosis.
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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.