Evidence map›Paper›PMID 15024039›Full record

ArticleThe Journal of general physiology2004

Differential effects of tyrosine kinase inhibitors on volume-sensitive chloride current in human atrial myocytes: evidence for dual regulation by Src and EGFR kinases.

Xin-Ling Du, Zhan Gao, Chu-Pak Lau, Shui-Wah Chiu, Hung-Fat Tse, Clive M Baumgarten, Gui-Rong Li

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In one paragraph

Article in The Journal of general physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

26 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
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  4. Tyrphostin AG556 increases the activity of large conductance CaJournal of cellular and molecular medicine · 2017
    Article
  5. Article
  6. Protein kinase C enhances the swelling-induced chloride current in human atrial myocytes.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016
    Article
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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

7 authors at 3 institutions in 3 countries.

Xin-Ling DuInstitute of Cardiovascular Science and Medicine/Department of Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Zhan Gao
Chu-Pak Lau
Shui-Wah Chiu
Hung-Fat Tse
Clive M Baumgarten
Gui-Rong Li
Grantham Hospital · CNUniversity of Hong Kong · HKVirginia Commonwealth University Medical Center · US

Funding

CARDIAC CELL VOLUME REGULATION IN HEALTH AND DISEASER01HL046764 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI BAUMGARTEN, CLIVE M · 1991 to 2004
$1.4M
NHLBI NIH HHS HL46764NHLBI NIH HHS R01 HL046764
6 · The paper itself

Abstract

To determine whether protein tyrosine kinase (PTK) modulates volume-sensitive chloride current (I(Cl.vol)) in human atrial myocytes and to identify the PTKs involved, we studied the effects of broad-spectrum and selective PTK inhibitors and the protein tyrosine phosphatase (PTP) inhibitor orthovanadate (VO(4)(-3)). I(Cl.vol) evoked by hyposmotic bath solution (0.6-times isosmotic, 0.6T) was enhanced by genistein, a broad-spectrum PTK inhibitor, in a concentration-dependent manner (EC(50) = 22.4 microM); 100 microM genistein stimulated I(Cl.vol) by 122.4 +/- 10.6%. The genistein-stimulated current was inhibited by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 150 microM) and tamoxifen (20 microM), blockers of I(Cl.vol). Moreover, the current augmented by genistein was volume dependent; it was abolished by hyperosmotic shrinkage in 1.4T, and genistein did not activate Cl(-) current in 1T. In contrast to the stimulatory effects of genistein, 100 microM tyrphostin A23 (AG 18) and A25 (AG 82) inhibited I(Cl.vol) by 38.2 +/- 4.9% and 40.9 +/- 3.4%, respectively. The inactive analogs, daidzein and tyrphostin A63 (AG 43), did not alter I(Cl.vol). In addition, the PTP inhibitor VO(4)(-3) (1 mM) reduced I(Cl.vol) by 53.5 +/- 4.5% (IC(50) = 249.6 microM). Pretreatment with VO(4)(-3) antagonized genistein-induced augmentation and A23- or A25-induced suppression of I(Cl.vol). Furthermore, the selective Src-family PTK inhibitor PP2 (5 microM) stimulated I(Cl.vol), mimicking genistein, whereas the selective EGFR (ErbB-1) kinase inhibitor tyrphostin B56 (AG 556, 25 microM) reduced I(Cl.vol), mimicking A23 and A25. The effects of both PP2 and B56 also were substantially antagonized by pretreatment with VO(4)(-3). The results suggest that I(Cl.vol) is regulated in part by the balance between PTK and PTP activity. Regulation is complex, however. Src and EGFR kinases, distinct soluble and receptor-mediated PTK families, have opposing effects on I(Cl.vol), and multiple target proteins are likely to be involved.

Indexed as

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAdultAgedChloride ChannelsChloridesDrug InteractionsEnzyme InhibitorsErbB ReceptorsGenisteinHeart AtriaHumansMembrane PotentialsMiddle AgedMyocytes, CardiacPhosphorylationProtein-Tyrosine Kinases4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidChloride ChannelsChloridesEnzyme InhibitorsErbB ReceptorsGenisteinProtein-Tyrosine Kinasessrc-Family KinasesTyrphostinsVanadates

Identifiers

PMID15024039
PMCPMC2217456
OpenAlexW2153676419

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.