Evidence map›Paper›PMID 26041446›Full record

ArticleAmerican journal of physiology. Renal physiology2015

Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3.

Devishree Krishnan, Lei Liu, Shane A Wiebe, Joseph R Casey, Emmanuelle Cordat, R Todd Alexander

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 49 citations in OpenAlex.

  1. Trial
  2. Article
  3. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025
    Article
  4. Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. New functions and roles of the NaPflugers Archiv : European journal of physiology · 2024
    Review
  9. Carbonic anhydrase, its inhibitors and vascular function.Frontiers in molecular biosciences · 2024
    Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Modulation of Tubular pH by Acetazolamide in a CaInternational journal of molecular sciences · 2021
    Article
  17. Article
  18. Acetazolamide causes renalAmerican journal of physiology. Renal physiology · 2020
    Article
  19. Article
  20. OATP1B3 Expression and Function is Modulated by Coexpression with OCT1, OATP1B1, and NTCP.Drug metabolism and disposition: the biological fate of chemicals · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Devishree KrishnanDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta, Canada; and.
Lei LiuDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada;
Shane A WiebeDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta, Canada; and.
Joseph R CaseyDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta, Canada; and.
Emmanuelle CordatDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta, Canada; and.
R Todd AlexanderDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Edmonton, Alberta, Canada; and Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada todd2@ualberta.ca.
University of Alberta · CA

Funding

CIHR 106464-1CIHR 106464-2CIHR 136891-1CIHR 96175-1CIHR 96175-2CIHR MOP106464CIHR MOP106565CIHR MOP123452
6 · The paper itself

Abstract

Two-thirds of sodium filtered by the renal glomerulus is reabsorbed from the proximal tubule via a sodium/proton exchanger isoform 3 (NHE3)-dependent mechanism. Since sodium and bicarbonate reabsorption are coupled, we postulated that the molecules involved in their reabsorption [NHE3 and carbonic anhydrase II (CAII)] might physically and functionally interact. Consistent with this, CAII and NHE3 were closely associated in a renal proximal tubular cell culture model as revealed by a proximity ligation assay. Direct physical interaction was confirmed in solid-phase binding assays with immobilized CAII and C-terminal NHE3 glutathione-S-transferase fusion constructs. To assess the effect of CAII on NHE3 function, we expressed NHE3 in a proximal tubule cell line and measured NHE3 activity as the rate of intracellular pH recovery, following an acid load. NHE3-expressing cells had a significantly greater rate of intracellular pH recovery than controls. Inhibition of endogenous CAII activity with acetazolamide significantly decreased NHE3 activity, indicating that CAII activates NHE3. To ascertain whether CAII binding per se activates NHE3, we expressed NHE3 with wild-type CAII, a catalytically inactive CAII mutant (CAII-V143Y), or a mutant unable to bind other transporters (CAII-HEX). NHE3 activity increased upon wild-type CAII coexpression, but not in the presence of the CAII V143Y or HEX mutant. Together these studies support an association between CAII and NHE3 that alters the transporter's activity.

Indexed as

AnimalsBicarbonatesCarbonic Anhydrase IICarbonic Anhydrase InhibitorsCell LineHumansHydrogen-Ion ConcentrationImmunoprecipitationKidneyKineticsMutationOpossumsProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingRecombinant ProteinsBicarbonatesCarbonic Anhydrase IICarbonic Anhydrase InhibitorsRecombinant ProteinsSLC9A3 protein, humanSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen Exchangerscarbonic anhydrase IINHE3pHsodium

Identifiers

PMID26041446
PMCPMC4959884
OpenAlexW1828905764

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.