Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Signal Transduction Mechanism(s) Involved in Prostacyclin Production Elicited by Acetylcholine in Coronary Endothelial Cells of Rabbit Heart

H. Kan, Y. Ruan and K. U. Malik
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 113-122;
H. Kan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Y. Ruan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
K. U. Malik
  • 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

The purpose of this study was to elucidate the mechanism by which acetylcholine (ACh) promotes prostacyclin (PGI2) production in cultured coronary endothelial cells (CEC) of the rabbit heart. ACh-induced production of PGI2, measured as immunoreactive 6-keto-PGF1 α, was enhanced by increasing the extracellular calcium (Ca++) concentration and reduced by Ca++ depletion. The receptor-operated Ca++channel blocker SK&F96365, but not the voltage-dependent Ca++ channel blockers verapamil or nifedipine, attenuated ACh-induced 6-keto-PGF1 α production and the associated rise in cytosolic Ca++. Thapsigargin, which depleted Ca++ accumulation from the intracellular Ca++ store, did not prevent the ACh-induced rise in cytosolic Ca++. In the absence of extracellular Ca++, ACh and ATP increased cytosolic Ca++ but did not alter 6-keto-PGF1 α production. In permeabilized CEC, guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-S) but not ACh enhanced 6-keto-PGF1 α synthesis. ACh increased 6-keto-PGF1 α production in the presence of GTP-γ-S. These effects of GTP-γ-S were attenuated by guanosine 5′-O-(2-thiotriphosphate). In the absence of extracellular Ca++, ACh or ATP increased cytosolic Ca++ in cells permeabilized with β-escin and loaded with GTP-γ-S; this effect was attenuated by guanosine 5′-O-(2-thiotriphosphate). The effect of ATP but not ACh to mobilize intracellular Ca++ or increase 6-keto-PGF1 α was inhibited by pertussis toxin. The phospholipase C inhibitor D609, which attenuated ACh- and ATP-induced mobilization of intracellular Ca++, did not alter 6-keto-PGF1 α production. The NO synthase inhibitor N-monomethyl-arginine also failed to alter ACh-induced 6-keto-PGF1 α synthesis. These data suggest that, in CEC of the rabbit heart, ACh stimulates prostacyclin production via a pertussis toxin-insensitive G protein and by increasing the influx of extracellular Ca++ through a G protein-independent receptor-operated Ca++ channel.

Footnotes

  • Send reprint requests to: Dr. Kafait U. Malik, Professor of Pharmacology, Department of Pharmacology, College of Medicine, University of Tennessee, The Health Science Center, Memphis, TN 38163.

  • ↵1 This study was supported by United States Public Health Service-National Institutes of Health Grant 19134-23 from the National Heart, Lung and Blood Institute. This work was presented in part at the Annual FASEB Meeting, April 1994, Anaheim, CA.

  • ↵2 Current address: Department of Medicine, Section of Cardiology, West Virginia University Health Sciences Center, P.O. Box 9157, Morgantown, WV 26506.

  • ↵3 Current address: Department of Pharmacology, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-6260.

  • Abbreviations:
    ACh
    acetylcholine
    PGI2
    prostacyclin
    Ca++
    extracellular calcium
    cGMP
    cyclic guanosine monophosphate
    CEC
    coronary endothelial cells
    ROCC
    receptor-operated Ca++ channel
    AA
    arachidonic acid
    D609
    tricyclodecan-9-yl-xanthogenate
    NO
    nitric oxide
    FCCP
    carbonyl cyanide p-(tri-fluoromethoxy)phenyl-hydrazone
    ATP
    adenosine-5′-triphosphate
    PLC
    phospholipase C
    BSS
    balanced salt solution
    HBSS
    Hanks’ BSS
    mAChR
    muscarinic acetylcholine receptor
    • Received November 18, 1996.
    • Accepted March 31, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Signal Transduction Mechanism(s) Involved in Prostacyclin Production Elicited by Acetylcholine in Coronary Endothelial Cells of Rabbit Heart
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Signal Transduction Mechanism(s) Involved in Prostacyclin Production Elicited by Acetylcholine in Coronary Endothelial Cells of Rabbit Heart

H. Kan, Y. Ruan and K. U. Malik
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 113-122;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Signal Transduction Mechanism(s) Involved in Prostacyclin Production Elicited by Acetylcholine in Coronary Endothelial Cells of Rabbit Heart

H. Kan, Y. Ruan and K. U. Malik
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 113-122;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Methods
    • Results
    • Discussion
    • Acknowledgment
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Biosynthesis of Sulfidopeptide Leukotrienes Via the Transfer of Leukotriene A4 from Polymorphonuclear Cells to Bovine Retinal Pericytes
  • The Preclinical Pharmacological Profile of the Potent and Selective Leukotriene B4 Antagonist CP-195543
  • NO-Independent Vasodilation to Acetylcholine in the Rat Isolated Kidney Utilizes a Charybdotoxin-Sensitive, Intermediate-Conductance Ca++-Activated K+ Channel
Show more PROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Similar Articles

  • 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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics