Evidence map›Paper›PMID 24052273›Full record

ArticleGut2014

Chloride channel inhibition by a red wine extract and a synthetic small molecule prevents rotaviral secretory diarrhoea in neonatal mice.

Eun-A Ko, Byung-Ju Jin, Wan Namkung, Tonghui Ma, Jay R Thiagarajah, A S Verkman

Abstract readEvaluation Study
In one paragraph

Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Frontiers in cellular and infection microbiology · 2024
    Article
  9. Article
  10. Role of ANO1 in tumors and tumor immunity.Journal of cancer research and clinical oncology · 2022
    Review
  11. Review
  12. The diverse roles of TMEM16A CaJournal of advanced research · 2021
    Review
  13. The CaActa pharmaceutica Sinica. B · 2021
    Review
  14. Article
  15. Anoctamin 1/TMEM16A controls intestinal ClExperimental & molecular medicine · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018
    Review
  20. Rotavirus infection.Nature reviews. Disease primers · 2017
    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 4 institutions in 3 countries.

Eun-A KoDepartments of Medicine and Physiology, University of California, San Francisco, California, USA.
Byung-Ju JinDepartments of Medicine and Physiology, University of California, San Francisco, California, USA.
Wan NamkungCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
Tonghui MaDepartment of Physiology, Dalian Medical University, Dalian, China.
Jay R ThiagarajahDepartment of Gastroenterology, Hepatology and Nutrition, Children's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA.
A S VerkmanDepartments of Medicine and Physiology, University of California, San Francisco, California, USA.
University of California, San Francisco · USBoston Children's Hospital · USDalian Medical University · CNYonsei University · KR

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIAR37DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1999 to 2008
$4.2M
Application of Novel Optical Methods to Cell DynamicsR37EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2007 to 2016
$4.1M
Application of Novel Optical Methods to Cell DynamicsR01EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2006
$1.7M
WATER AND NON-ELECTROLYTE TRANSPORT IN RENAL VESICLESR01DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1986 to 2014
$1.4M
NEI NIH HHS EY13574NEI NIH HHS R01 EY013574NIBIB NIH HHS EB00415NIBIB NIH HHS R01 EB000415NIBIB NIH HHS R37 EB000415NIDDK NIH HHS DK35124NIDDK NIH HHS DK72517NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK035124NIDDK NIH HHS R37 DK035124
6 · The paper itself

Abstract

backgroundRotavirus is the most common cause of severe secretory diarrhoea in infants and young children globally. The rotaviral enterotoxin, NSP4, has been proposed to stimulate calcium-activated chloride channels (CaCC) on the apical plasma membrane of intestinal epithelial cells. We previously identified red wine and small molecule CaCC inhibitors.

objectiveTo investigate the efficacy of a red wine extract and a synthetic small molecule, CaCCinh-A01, in inhibiting intestinal CaCCs and rotaviral diarrhoea.

designInhibition of CaCC-dependent current was measured in T84 cells and mouse ileum. The effectiveness of an orally administered wine extract and CaCCinh-A01 in inhibiting diarrhoea in vivo was determined in a neonatal mouse model of rotaviral infection.

resultsScreening of ∼150 red wines revealed a Cabernet Sauvignon that inhibited CaCC current in T84 cells with IC50 at a ∼1:200 dilution, and higher concentrations producing 100% inhibition. A >1 kdalton wine extract prepared by dialysis, which retained full inhibition activity, blocked CaCC current in T84 cells and mouse intestine. In rotavirus-inoculated mice, oral administration of the wine extract prevented diarrhoea by inhibition of intestinal fluid secretion without affecting rotaviral infection. The wine extract did not inhibit the cystic fibrosis chloride channel (CFTR) in cell cultures, nor did it prevent watery stools in neonatal mice administered cholera toxin, which activates CFTR-dependent fluid secretion. CaCCinh-A01 also inhibited rotaviral diarrhoea.

conclusionsOur results support a pathogenic role for enterocyte CaCCs in rotaviral diarrhoea and demonstrate the antidiarrhoeal action of CaCC inhibition by an alcohol-free, red wine extract and by a synthetic small molecule.

Indexed as

WineAnimalsCell LineChloride ChannelsDiarrheaEnterocytesFluorescent Antibody TechniqueIleumIntestinal MucosaMiceMice, Inbred C57BLRotavirus InfectionsChloride ChannelsDiarrhoeaIntestinal SecretionIon Channels

Identifiers

PMID24052273
PMCPMC4048772
OpenAlexW2118936437

What OpenQuestion holds

Textmetadata
LicenceTDM
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.