Evidence map›Paper›PMID 20554763›Full record

ArticleMolecular biology of the cell2010

CFTR-adenylyl cyclase I association responsible for UTP activation of CFTR in well-differentiated primary human bronchial cell cultures.

Wan Namkung, Walter E Finkbeiner, A S Verkman

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

52 citing papers in PubMed, 74 citations in OpenAlex.

  1. Trial
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  10. Review
  11. Article
  12. Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia.American journal of respiratory and critical care medicine · 2021
    Article
  13. CLCA1 Regulates Airway Mucus Production and Ion Secretion Through TMEM16A.International journal of molecular sciences · 2021
    Article
  14. Review
  15. Purinergic receptors in airway hydration.Biochemical pharmacology · 2021
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia.American journal of physiology. Lung cellular and molecular physiology · 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

3 authors at 1 institution in 1 country.

Wan NamkungDepartment of Medicine and Physiology, University of California, San Francisco, CA 94143, USA.
Walter E Finkbeiner
A S Verkman
University of California, San Francisco · US

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
Role of ASL and Airway Glands in CF Lung DiseaseR01HL073856 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2003 to 2010
$3.1M
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
CFTR inhibitors for therapy of polycystic kidney diseaseRC1DK086125 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2009 to 2010
$989k
NEI NIH HHS EY13574NEI NIH HHS R01 EY013574NHLBI NIH HHS HL73856NHLBI NIH HHS R01 HL073856NIBIB NIH HHS EB00415NIBIB NIH HHS R01 EB000415NIBIB NIH HHS R37 EB000415NIDDK NIH HHS DK35124NIDDK NIH HHS DK72517NIDDK NIH HHS DK86125NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK035124NIDDK NIH HHS R37 DK035124NIDDK NIH HHS RC1 DK086125
6 · The paper itself

Abstract

Chloride secretion by airway epithelial cells is defective in cystic fibrosis (CF). The conventional paradigm is that CFTR is activated through cAMP and protein kinase A (PKA), whereas the Ca(2+)-activated chloride channel (CaCC) is activated by Ca(2+) agonists like UTP. We found that most chloride current elicited by Ca(2+) agonists in primary cultures of human bronchial epithelial cells is mediated by CFTR by a mechanism involving Ca(2+) activation of adenylyl cyclase I (AC1) and cAMP/PKA signaling. Use of selective inhibitors showed that Ca(2+) agonists produced more chloride secretion from CFTR than from CaCC. CFTR-dependent chloride secretion was reduced by PKA inhibition and was absent in CF cell cultures. Ca(2+) agonists produced cAMP elevation, which was blocked by adenylyl cyclase inhibition. AC1, a Ca(2+)/calmodulin-stimulated adenylyl cyclase, colocalized with CFTR in the cell apical membrane. RNAi knockdown of AC1 selectively reduced UTP-induced cAMP elevation and chloride secretion. These results, together with correlations between cAMP and chloride current, suggest that compartmentalized AC1-CFTR association is responsible for Ca(2+)/cAMP cross-talk. We further conclude that CFTR is the principal chloride secretory pathway in non-CF airways for both cAMP and Ca(2+) agonists, providing a novel mechanism to link CFTR dysfunction to CF lung disease.

Indexed as

Adenylyl CyclasesBronchiCalciumCell DifferentiationCell MembraneCell PolarityCells, CulturedChloridesCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorElectric ConductivityEnzyme ActivationEpithelial CellsHumansIon Channel GatingAdenylyl CyclasesCalciumChloridesCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorPotassium ChannelsUridine Triphosphate

Identifiers

PMID20554763
PMCPMC2912350
OpenAlexW2125281084

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.