Evidence map›Paper›PMID 9096337›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1997

cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein.

C H Yun, S Oh, M Zizak, D Steplock, S Tsao, C M Tse, E J Weinman, M Donowitz

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 164 papers.

0numbers the graph read from it
0cells of the map it votes in
164citing papers in PubMed
9.8field-weighted citation impact, top 1% 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

164 citing papers in PubMed, 424 citations in OpenAlex.

  1. Review
  2. Article
  3. Zinc inhibits cAMP-induced ClAmerican journal of physiology. Cell physiology · 2025
    Article
  4. Histamine regulates the activity and the expression of the NaInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  5. Review
  6. The Molecular Biology of Placental Transport of Calcium to the Human Foetus.International journal of molecular sciences · 2025
    Review
  7. Actin cytoskeleton and associated myosin motors within the renal epithelium.American journal of physiology. Renal physiology · 2024
    Review
  8. Article
  9. Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024
    Article
  10. Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas.Translational research : the journal of laboratory and clinical medicine · 2024
    Article
  11. Inhibition of protein kinase C-α and activation of ezrin byAmerican journal of physiology. Endocrinology and metabolism · 2023
    Article
  12. Article
  13. ERM-1 Phosphorylation and NRFL-1 Redundantly Control Lumen Formation in theFrontiers in cell and developmental biology · 2022
    Article
  14. Review
  15. Article
  16. The NaFrontiers in physiology · 2022
    Review
  17. Review
  18. Article
  19. Article
  20. Decreased Brain pH and Pathophysiology in Schizophrenia.International journal of molecular sciences · 2021
    Review

104 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

C H YunDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. cyun@welchlink.welch.jhu.edu
S Oh
M Zizak
D Steplock
S Tsao
C M Tse
E J Weinman
M Donowitz
Johns Hopkins University · USWest Virginia University · US

Funding

DIARRHEAL DISEASES: A PHYSIOLOGIC APPROACH TO TREATMENTR01DK026523 · NIDDK · TUFTS MEDICAL CENTER · PI DONOWITZ, MARK · 1986 to 2016
$7.8M
STRUCTURE AND FUNCTION STUDIES OF CLONED SODIUM AND HYDROGEN EXCHANGERSP01DK044484 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI MONTROSE, MARSHALL H · 1992 to 2002
$2.6M
STRUCTURE/FUNCTION STUDIES NA/H EXCHANGER INFORM (NHE3)F05TW005234 · FIC · JOHNS HOPKINS UNIVERSITY · PI ZIZAK, MIRZA · 1995 to 1996
–
STRUCTURE/FUNCTION STUDIES OF CLONED NA+/H+ EXCHANGERSF32DK008950 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI YUN, CHANGHYON CHRIS · 1993 to 1994
–
FIC NIH HHS F05 TW005234NIDDK NIH HHS DK08950NIDDK NIH HHS DK 26523NIDDK NIH HHS DK44484NIDDK NIH HHS R01 DK026523
6 · The paper itself

Abstract

NHE3 is the Na+/H+ exchanger located on the intestinal and renal brush border membrane, where it functions in transepithelial Na+ absorption. The brush border Na+ absorptive process is acutely inhibited by activation of cAMP-dependent protein kinase, but the molecular mechanism of this inhibitory effect is poorly understood. We have identified two regulatory proteins, E3KARP and NHERF, that interact with NHE3 to enable cAMP to inhibit NHE3. The two regulatory proteins are structurally related, sharing approximately 50% identity in amino acid sequences. It has been previously shown that when NHE3 is transfected into PS120 fibroblasts or Caco-2 cells, cAMP failed to inhibit NHE3 activity. Northern blot analysis showed that both PS120 and Caco-2 cells lacked the expression of both E3KARP and NHERF. In contrast, other cell lines in which cAMP inhibits NHE3, including OK, CHO, and LLC-PK1 cells, expressed NHERF-related regulatory proteins. To determine their functions in cAMP-dependent inhibition of NHE3, E3KARP and NHERF were transfected into PS120/NHE3 fibroblasts. Transfection in PS120/NHE3 fibroblasts with either NHERF or E3KARP reconstituted cAMP-induced inhibition of NHE3, resulting in 25-30% inhibition in these cells.

Indexed as

Amino Acid SequenceAnimalsCell LineCyclic AMPCyclic AMP-Dependent Protein KinasesEpitheliumHumansIntestinal MucosaKidneyMicrovilliMolecular Sequence DataRabbitsRNA, MessengerSequence Homology, Amino AcidSodium-Hydrogen ExchangersCyclic AMPCyclic AMP-Dependent Protein KinasesRNA, MessengerSodium-Hydrogen Exchangers

Identifiers

PMID9096337
PMCPMC20313
OpenAlexW2027935874

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.