ArticleAmerican journal of physiology. Renal physiology2016
Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.
Article in American journal of physiology. Renal physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Effects of proximal tubule NBCe1-A deletion on collecting duct intercalated cell responses to hypokalemia.American journal of physiology. Renal physiology · 2026Article
- Renal NHE3 is required to limit hypokalemia and metabolic acidosis during dietary potassium deficiency.Pflugers Archiv : European journal of physiology · 2026Article
- Lack of a role of NHE4 in renal ammonia metabolism.American journal of physiology. Renal physiology · 2025Article
- Role of KThe American journal of pathology · 2025Article
- Sex differences in renal transporters: assessment and functional consequences.Nature reviews. Nephrology · 2024Review
- The proximal tubule through an NBCe1-dependent mechanism regulates collecting duct phenotypic and remodeling responses to acidosis.American journal of physiology. Renal physiology · 2023Article
- Acid-base effects of combined renal deletion of NBCe1-A and NBCe1-B.American journal of physiology. Renal physiology · 2022Article
- Role of the renal androgen receptor in sex differences in ammonia metabolism.American journal of physiology. Renal physiology · 2021Article
- Acetazolamide causes renalAmerican journal of physiology. Renal physiology · 2020Article
- Testosterone modulates renal ammonia metabolism.American journal of physiology. Renal physiology · 2020Article
- NBCe1-A is required for the renal ammonia and KAmerican journal of physiology. Renal physiology · 2020Article
- Differences in acidosis-stimulated renal ammonia metabolism in the male and female kidney.American journal of physiology. Renal physiology · 2019Article
- Regulation of renal NaDC1 expression and citrate excretion by NBCe1-A.American journal of physiology. Renal physiology · 2019Article
- Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance.Seminars in nephrology · 2019Review
- Expression of the B splice variant of NBCe1 (SLC4A4) in the mouse kidney.American journal of physiology. Renal physiology · 2018Article
- Differences in renal ammonia metabolism in male and female kidney.American journal of physiology. Renal physiology · 2018Article
- Mechanism of Hyperkalemia-Induced Metabolic Acidosis.Journal of the American Society of Nephrology : JASN · 2018Article
- NBCe1-A Regulates Proximal Tubule Ammonia Metabolism under Basal Conditions and in Response to Metabolic Acidosis.Journal of the American Society of Nephrology : JASN · 2018Article
- Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction.American journal of physiology. Renal physiology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.
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Registered trials
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