Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Potent Activation of Large-Conductance Ca2+-Activated K+ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH3) Cells

Sheng-Nan Wu, Hsung Peng, Bing-Shuo Chen, Ya-Jean Wang, Pei-Yu Wu and Ming-Wei Lin
Molecular Pharmacology December 2008, 74 (6) 1696-1704; DOI: https://doi.org/10.1124/mol.108.049106
Sheng-Nan Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hsung Peng
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bing-Shuo Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ya-Jean Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pei-Yu Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ming-Wei Lin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) is reported to be an activator of human ether-à-go-go-related gene current. However, it remains unknown whether it has any effects on other types of ion channels. The effects of NS1643 on ion currents and membrane potential were investigated in this study. NS1643 stimulated Ca2+-activated K+ current [IK(Ca)] in a concentration-dependent manner with an EC50 value of 1.8 μM in pituitary tumor (GH3) cells. In inside-out recordings, this compound applied to the intracellular side of the detached channels stimulated large-conductance Ca2+-activated K+ (BKCa) channels with no change in single-channel conductance. It shifted the activation curve of BKCa channels to less depolarized voltages without altering the gating charge of the channels. NS1643-stimulated channel activity depended on intracellular Ca2+, and mean closed time during exposure to NS1643 was reduced. NS1643 (3 μM) had little or no effect on peak amplitude of ether-à-go-go-related gene-mediated K+ current evoked by membrane hyperpolarization, although it increased the amplitude of late-sustained components of K+ inward current, which was suppressed by paxilline but not by azimilide. NS1643 (3 μM) had no effect on L-type Ca2+ current. This compound reduced repetitive firing of action potentials, and further application of paxilline attenuated its decrease in firing rate. In addition, NS1643 enhanced BKCa-channel activity in human embryonic kidney 293T cells expressing α-hSlo. In summary, we clearly show that NS1643 interacts directly with the BKCa channel to increase the amplitude of IK(Ca) in pituitary tumor (GH3) cells. The α-subunit of the channel may be a target for the action of this small compound.

Footnotes

  • The work in this laboratory was partly supported by grants from the National Science Council (NSC-95-2745-B-006-002-MY2) and the Program for Promoting Academic Excellence and Developing World Class Research Centers, Ministry of Education, Taiwan. H.P., M.L. and Y.W. were partially supported by Graduate Scholarships from National Cheng Kung University Medical College.

  • ABBREVIATIONS: AP, action potential; BKCa, large-conductance Ca2+-activated K+; erg, ether-à-go-go related gene; HEK, human embryonic kidney; HERG, human ether-à-go-go-related gene; hSlo, human slowpoke; IK(Ca), Ca2+-activated K+ current; IK(erg), ether-à-go-go related gene-mediated K+ current; NS1608, N-(3-(trifluoromethyl)phenyl)-N′-(2-hydroxy-5-chlorophenyl)urea; PEI, polyethylenimine.

  • ↵ Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

    • Received May 23, 2008.
    • Accepted September 22, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 74 (6)
Molecular Pharmacology
Vol. 74, Issue 6
1 Dec 2008
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Potent Activation of Large-Conductance Ca2+-Activated K+ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH3) Cells
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Potent Activation of Large-Conductance Ca2+-Activated K+ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH3) Cells

Sheng-Nan Wu, Hsung Peng, Bing-Shuo Chen, Ya-Jean Wang, Pei-Yu Wu and Ming-Wei Lin
Molecular Pharmacology December 1, 2008, 74 (6) 1696-1704; DOI: https://doi.org/10.1124/mol.108.049106

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Potent Activation of Large-Conductance Ca2+-Activated K+ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH3) Cells

Sheng-Nan Wu, Hsung Peng, Bing-Shuo Chen, Ya-Jean Wang, Pei-Yu Wu and Ming-Wei Lin
Molecular Pharmacology December 1, 2008, 74 (6) 1696-1704; DOI: https://doi.org/10.1124/mol.108.049106
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Cysteine151 in Keap1 Drives CDDO-Me Pharmacodynamic Action
  • Allosteric Modulation of Metabotropic Glutamate Receptor 1
  • Mechanism of Selective Action of Paraherquamide A
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics