Evidence map›Paper›PMID 10545138›Full record

ArticleThe Journal of physiology1999

Inhibition of Na+-H+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum.

M Gekle, K Drumm, S Mildenberger, R Freudinger, B Gassner, S Silbernagl

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In one paragraph

Article in The Journal of physiology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed, 114 citations in OpenAlex.

  1. Cystinosin regulates NaEMBO reports · 2026
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  5. Cystinosin is involved in NabioRxiv : the preprint server for biology · 2025
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  10. Review
  11. Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Proximal tubular NHEs: sodium, protons and calcium?American journal of physiology. Renal physiology · 2013
    Review
  17. Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by extracellular signal-regulated kinase 1/2.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2012
    Article
  18. Article
  19. Article
  20. Review
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.

M GeklePhysiologisches Institut, University of Würzburg, Würzburg, Germany. michael.gekle@mail.uni-wuerzburg.de
K Drumm
S Mildenberger
R Freudinger
B Gassner
S Silbernagl
University of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

1. Receptor-mediated endocytosis is an important mechanism for transport of macromolecules and regulation of cell-surface receptor expression. In renal proximal tubules, receptor-mediated endocytosis mediates the reabsorption of filtered albumin. Acidification of the endocytic compartments is essential because it interferes with ligand-receptor dissociation, vesicle trafficking, fusion events and coat formation. 2. Here we show that the activity of Na+-H+ exchanger isoform 3 (NHE3) is important for proper receptor-mediated endocytosis of albumin and endosomal pH homeostasis in a renal proximal tubular cell line (opossum kidney cells) which expresses NHE3 only. 3. Depending on their inhibitory potency with respect to NHE3 and their lipophilicity, the NHE inhibitors EIPA, amiloride and HOE694 differentially reduced albumin endocytosis. The hydrophilic inhibitor HOE642 had no effect. 4. Inhibition of NHE3 led to an alkalinization of early endosomes and to an acidification of the cytoplasm, indicating that Na+-H+ exchange contributes to the acidification of the early endosomal compartment due to the existence of a sufficient Na+ gradient across the endosomal membrane. 5. Exclusive acidification of the cytoplasm with propionic acid or by removal of Na+ induced a significantly smaller reduction in endocytosis than that induced by inhibition of Na+-H+ exchange. 6. Analysis of the inhibitory profiles indicates that in early endosomes and endocytic vesicles NHE3 is of major importance, whereas plasma membrane NHE3 plays a minor role. 7. Thus, NHE3-mediated acidification along the first part of the endocytic pathway plays an important role in receptor-mediated endocytosis. Furthermore, the involvement of NHE3 offers new ways to explain the regulation of receptor-mediated endocytosis.

Indexed as

AmilorideAnimalsBinding SitesCell MembraneCytosolEndocytosisEndosomesEpithelial CellsGuanidinesHydrogen-Ion ConcentrationKidney Tubules, ProximalLysosomesOpossumsPropionatesReceptors, Cell SurfaceSerum Albumin3-methylsulfonyl-4-piperidinobenzoyl guanidineAmiloridecariporideethylisopropylamilorideGuanidinesPropionatespropionic acidReceptors, Cell SurfaceSerum AlbuminSodiumSodium-Hydrogen ExchangersSulfones

Identifiers

PMID10545138
PMCPMC2269612
OpenAlexW1968788071

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.