ReviewAmerican journal of physiology. Renal physiology2011
Molecular regulation of NKCC2 in the thick ascending limb.
Review in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 185 citations in OpenAlex.
- Renal effects of short-term ketone monoester supplementation in healthy adults: A randomized, placebo-controlled study.Physiological reports · 2026Trial
- Effect of furosemide on body composition and urinary proteins that mediate tubular sodium and sodium transport-A randomized controlled trial.Physiological reports · 2021Trial
- Adjunctive acetazolamide therapy for the treatment of Bartter syndrome.International urology and nephrology · 2020Trial
- Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders.Translational psychiatry · 2017Trial
- Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls.BMC nephrology · 2014Trial
- Genome-wide association study of molecular markers related to keel length in a specialized strain of yellow feathered broilers.Poultry science · 2026Article
- The non-steroidal mineralocorticoid receptor blocker esaxerenone reduces glomerular hyperfiltration and albuminuria.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians.International journal of molecular sciences · 2026Review
- How Does Dietary Potassium Influence BP?Journal of the American Society of Nephrology : JASN · 2026Review
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- Calcium-binding protein 39 in with-no-lysine kinase signaling and the modulation of renal tubular transport.Current opinion in nephrology and hypertension · 2025Review
- Genome-Wide Identification of Solute Carrier Family 12 and Functional Characterization of Its Role in Saline-Alkaline Stress Acclimation in the Ridgetail White ShrimpInternational journal of molecular sciences · 2025Article
- Ammonia transport mediated by urea transporter A isoforms.Biology open · 2025Article
- Urinary sodium wasting and disrupted collecting duct function in mice with distal renal tubular acidosis mutations.Disease models & mechanisms · 2025Article
- Stuck in Traffic-Myosin Motors Ease Gridlock in the Loop.Function (Oxford, England) · 2025Article
- The FSGS protein actinin-4 interacts with NKCC2 to regulate thick ascending limb NaCl reabsorption.American journal of physiology. Renal physiology · 2024Article
- Actin cytoskeleton and associated myosin motors within the renal epithelium.American journal of physiology. Renal physiology · 2024Review
- Review
- Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions.Frontiers in physiology · 2024Review
- [Mechanisms of action and clinical application of diuretics in intensive care medicine].Die Anaesthesiologie · 2023Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The kidney plays an essential role in blood pressure regulation by controlling short-term and long-term NaCl and water balance. The thick ascending limb of the loop of Henle (TAL) reabsorbs 25-30% of the NaCl filtered by the glomeruli in a process mediated by the apical Na(+)-K(+)-2Cl(-) cotransporter NKCC2, which allows Na(+) and Cl(-) entry from the tubule lumen into TAL cells. In humans, mutations in the gene coding for NKCC2 result in decreased or absent activity characterized by severe salt and volume loss and decreased blood pressure (Bartter syndrome type 1). Opposite to Bartter's syndrome, enhanced NaCl absorption by the TAL is associated with human hypertension and animal models of salt-sensitive hypertension. TAL NaCl reabsorption is subject to exquisite control by hormones like vasopressin, parathyroid, glucagon, and adrenergic agonists (epinephrine and norepinephrine) that stimulate NaCl reabsorption. Atrial natriuretic peptides or autacoids like nitric oxide and prostaglandins inhibit NaCl reabsorption, promoting salt excretion. In general, the mechanism by which hormones control NaCl reabsorption is mediated directly or indirectly by altering the activity of NKCC2 in the TAL. Despite the importance of NKCC2 in renal physiology, the molecular mechanisms by which hormones, autacoids, physical factors, and intracellular ions regulate NKCC2 activity are largely unknown. During the last 5 years, it has become apparent that at least three molecular mechanisms determine NKCC2 activity. As such, membrane trafficking, phosphorylation, and protein-protein interactions have recently been described in TALs and heterologous expression systems as mechanisms that modulate NKCC2 activity. The focus of this review is to summarize recent data regarding NKCC2 regulation and discuss their potential implications in physiological control of TAL function, renal physiology, and blood pressure regulation.
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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.