ArticleThe Journal of biological chemistry2013
Haploinsufficiency of the ammonia transporter Rhcg predisposes to chronic acidosis: Rhcg is critical for apical and basolateral ammonia transport in the mouse collecting duct.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- WDR72 Is Required for Urinary Acidification and Normal HActa physiologica (Oxford, England) · 2026Article
- State of knowledge on ammonia handling by the kidney.Pflugers Archiv : European journal of physiology · 2024Review
- Role of the renal androgen receptor in sex differences in ammonia metabolism.American journal of physiology. Renal physiology · 2021Article
- Testosterone modulates renal ammonia metabolism.American 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
- Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.Seminars in nephrology · 2019Review
- Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance.Seminars in nephrology · 2019Review
- Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis.Journal of nephrology · 2018Review
- 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
- The ammonia transporter RhCG modulates urinary acidification by interacting with the vacuolar proton-ATPases in renal intercalated cells.Kidney international · 2018Article
- Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead.Pediatric health, medicine and therapeutics · 2018Review
- Ammonia Transporters and Their Role in Acid-Base Balance.Physiological reviews · 2017Review
- Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney.Pflugers Archiv : European journal of physiology · 2016Article
- Renal acid-base regulation: new insights from animal models.Pflugers Archiv : European journal of physiology · 2015Review
- Effect of dietary protein restriction on renal ammonia metabolism.American journal of physiology. Renal physiology · 2015Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
- The role of the renal ammonia transporter Rhcg in metabolic responses to dietary protein.Journal of the American Society of Nephrology : JASN · 2014Article
- Ammonia transport in the kidney by Rhesus glycoproteins.American journal of physiology. Renal physiology · 2014Review
- Effect of collecting duct-specific deletion of both Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg) on renal response to metabolic acidosis.American journal of physiology. Renal physiology · 2014Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ammonia secretion by the collecting duct (CD) is critical for acid-base homeostasis and, when defective, causes distal renal tubular acidosis (dRTA). The Rhesus protein RhCG mediates NH(3) transport as evident from cell-free and cellular models as well as from Rhcg-null mice. Here, we investigated in a Rhcg mouse model the metabolic effects of Rhcg haploinsufficiency, the role of Rhcg in basolateral NH(3) transport, and the mechanisms of adaptation to the lack of Rhcg. Both Rhcg(+/+) and Rhcg(+/-) mice were able to handle an acute acid load, whereas Rhcg(-/-) mice developed severe metabolic acidosis with reduced ammonuria and high mortality. However, chronic acid loading revealed that Rhcg(+/-) mice did not fully recover, showing lower blood HCO(3)(-) concentration and more alkaline urine. Microperfusion studies demonstrated that transepithelial NH(3) permeability was reduced by 80 and 40%, respectively, in CDs from Rhcg(-/-) and Rhcg(+/-) mice compared with controls. Basolateral membrane permeability to NH(3) was reduced in CDs from Rhcg(-/-) mice consistent with basolateral Rhcg localization. Rhcg(-/-) responded to acid loading with normal expression of enzymes and transporters involved in proximal tubular ammoniagenesis but reduced abundance of the NKCC2 transporter responsible for medullary accumulation of ammonium. Consequently, tissue ammonium content was decreased. These data demonstrate a role for apical and basolateral Rhcg in transepithelial NH(3) transport and uncover an incomplete dRTA phenotype in Rhcg(+/-) mice. Haploinsufficiency or reduced expression of RhCG may underlie human forms of (in)complete dRTA.
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