ArticleAmerican journal of physiology. Renal physiology2008
cGMP decreases surface NKCC2 levels in the thick ascending limb: role of phosphodiesterase 2 (PDE2).
Article in American journal of physiology. Renal physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 55 citations in OpenAlex.
- 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
- Nitric oxide mediates ET-1-induced-inhibition of NPPB-sensitive ClThe Journal of biological chemistry · 2026Article
- 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
- Cyclic Adenosine Monophosphate Signaling in Chronic Kidney Disease: Molecular Targets and Therapeutic Potentials.International journal of molecular sciences · 2024Review
- Update on NKCC2 regulation in the thick ascending limb (TAL) by membrane trafficking, phosphorylation, and protein-protein interactions.Frontiers in physiology · 2024Review
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase family in the thick ascending limb of the loop of Henle.American journal of physiology. Renal physiology · 2023Article
- Nitric oxide-inhibited chloride transport in cortical thick ascending limbs is reversed by 8-iso-prostaglandin-F2α.Kidney research and clinical practice · 2022Article
- Molecular characteristics and physiological roles of NaJournal of cellular physiology · 2021Review
- Molecular regulation of NKCC2 in blood pressure control and hypertension.Current opinion in nephrology and hypertension · 2019Review
- Superoxide increases surface NKCC2 in the rat thick ascending limbs via PKC.American journal of physiology. Renal physiology · 2019Article
- Fructose acutely stimulates NKCC2 activity in rat thick ascending limbs by increasing surface NKCC2 expression.American journal of physiology. Renal physiology · 2019Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Effects of Reactive Oxygen Species on Tubular Transport along the Nephron.Antioxidants (Basel, Switzerland) · 2017Review
- Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE.The Journal of biological chemistry · 2016Article
- Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension.Current hypertension reports · 2016Review
- Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron.Cell metabolism · 2016Article
- ANP-induced signaling cascade and its implications in renal pathophysiology.American journal of physiology. Renal physiology · 2015Review
- Vesicle-associated membrane protein 2 (VAMP2) but Not VAMP3 mediates cAMP-stimulated trafficking of the renal Na+-K+-2Cl- co-transporter NKCC2 in thick ascending limbs.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
NaCl absorption in the medullary thick ascending limb of the loop of Henle (THAL) is mediated by the apical Na/K/2Cl cotransporter (NKCC2). Hormones that increase cGMP, such as nitric oxide (NO) and natriuretic peptides, decrease NaCl absorption by the THAL. However, the mechanism by which cGMP decreases NaCl absorption in THALs is not known. We hypothesized that cGMP decreases surface NKCC2 levels in the THAL. We used surface biotinylation to measure surface NKCC2 levels in rat THAL suspensions. We tested the effect of the membrane-permeant cGMP analog dibutyryl-cGMP (db-cGMP) on surface NKCC2 levels. Incubating THALs with db-cGMP for 20 min decreased surface NKCC2 levels in a concentration-dependent manner (basal=100%; db-cGMP 100 microM=77+/-7%; 500 microM=54+/-10% and 1,000 microM=61+/-8%). A different cGMP analog 8-bromo-cGMP (8-Br-cGMP) also decreased surface NKCC2 levels by 25%, (basal=100%; 8-Br-cGMP=75+/-5%). Incubation of isolated, perfused THALs with db-cGMP decreased apical surface NKCC2 labeling levels as measured by immunofluorescence and confocal microscopy. cGMP-stimulated phosphodiesterase 2 (PDE2) mediates the inhibitory effect of NO on NaCl absorption by THALs. Thus we examined the role of PDE2 and found that PDE2 inhibitors blocked the effect of db-cGMP on surface NKCC2. Also, a nonstimulatory concentration of db-cAMP blocked the cGMP-induced decrease in surface NKCC2. Finally, db-cGMP inhibited THAL net Cl absorption by 48+/-4%, and this effect was completely blocked by PDE2 inhibition. We conclude that cGMP decreases NKCC2 levels in the apical membrane of THALs and that this effect is mediated by PDE2. This is an important mechanism by which cGMP inhibits NaCl absorption by the THAL.
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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.