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
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
    • 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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction

Alan S. Braverman, Anil K. Vegesna, Larry S. Miller, Mary F. Barbe, Mansoor Tiwana, Kashif Hussain and Michael R. Ruggieri Sr
Journal of Pharmacology and Experimental Therapeutics July 2011, 338 (1) 37-46; DOI: https://doi.org/10.1124/jpet.110.177097
Alan S. Braverman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anil K. Vegesna
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Larry S. Miller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mary F. Barbe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mansoor Tiwana
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kashif Hussain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael R. Ruggieri Sr
  • 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 + SI
  • PDF
Loading

Abstract

Relaxation of gastric clasp and sling muscle fibers is involved the transient lower esophageal sphincter relaxations underlying the pathophysiology of gastroesophageal reflux disease (GERD). These fibers do not contribute tone to the high-pressure zone in GERD patients, indicating their role in pathophysiology. This study identifies some mediators of the nicotine-induced relaxation of muscarinic receptor precontracted gastric clasp and sling fibers. Muscle strips from organ donors precontracted with bethanechol were relaxed with nicotine and then rechallenged after washing and adding inhibitors tetrodotoxin (TTX), the nitric-oxide synthase inhibitor l-nitro-arginine methyl ester (l-NAME), the β-adrenoceptor antagonist propranolol, the glycine receptor antagonist strychnine or ginkgolide B, and the GABAA receptor antagonist bicuculline or 2-(3-carboxypropyl)-3-amino-6-(4 methoxyphenyl)pyridazinium bromide [(gabazine) SR95531]. TTX only inhibited clasp fiber relaxations. l-NAME and propranolol inhibited, and ginkgolide B was ineffective in both. SR95531 was ineffective in clasp fibers and partially effective in sling fibers. Strychnine and bicuculline prevented relaxations with low potency, indicating actions not on glycine or GABAA receptors but more consistent with nicotinic receptor blockade. Bethanechol-precontracted fibers were relaxed by the nitric oxide donor S-nitroso-N-acetyl-dl-penicillamine and by the β-adrenergic agonist isoproterenol (clasp fibers only) but not by the glycine receptor agonist taurine or glycine or the GABAA agonist muscimol. These data indicate that nicotinic receptor activation mediates relaxation via release of nitric oxide in clasp and sling fibers, norepinephrine acting on β-adrenoceptors in clasp fibers, and GABA acting on GABAA receptors in sling fibers. Agents that selectively prevent these relaxations may be useful in the treatment of GERD.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK059500]; and the Investigator-Sponsored Study Program of AstraZeneca.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.177097.

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

  • ABBREVIATIONS:

    TLESR
    transient lower esophageal sphincter relaxation
    BIC
    bicuculline
    CGRP
    calcitonin gene-related polypeptide
    CO
    carbon monoxide
    EFS
    electric field stimulation
    GEJ
    gastroesophageal junction
    GERD
    gastroesophageal reflux disease
    HPZ
    high-pressure zone
    LEC
    lower esophageal circular muscle
    LES
    lower esophageal sphincter
    l-NAME
    l-nitro-arginine methyl ester
    NIC
    nicotine
    NOS
    nitric-oxide synthase
    PACAP
    pituitary adenylate cyclase-activating peptide
    PROP
    propranolol
    SNAP
    S-nitroso-N-acetyl-dl-penicillamine
    STRY
    strychnine
    TTX
    tetrodotoxin
    SR95531
    2-(3-carboxypropyl)-3-amino-6-(4 methoxyphenyl)pyridazinium bromide (gabazine)
    VIP
    vasoactive intestinal polypeptide.

  • Received November 8, 2010.
  • Accepted March 31, 2011.
  • Copyright © 2011 by 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: 338 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 338, Issue 1
1 Jul 2011
  • 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 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.
Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction
(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
Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction

Alan S. Braverman, Anil K. Vegesna, Larry S. Miller, Mary F. Barbe, Mansoor Tiwana, Kashif Hussain and Michael R. Ruggieri
Journal of Pharmacology and Experimental Therapeutics July 1, 2011, 338 (1) 37-46; DOI: https://doi.org/10.1124/jpet.110.177097

Citation Manager Formats

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

Share
Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction

Alan S. Braverman, Anil K. Vegesna, Larry S. Miller, Mary F. Barbe, Mansoor Tiwana, Kashif Hussain and Michael R. Ruggieri
Journal of Pharmacology and Experimental Therapeutics July 1, 2011, 338 (1) 37-46; DOI: https://doi.org/10.1124/jpet.110.177097
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CGRP Signaling in Visceral Organ Cross-Sensitization
  • Peptide AIP Alleviates Renal Fibrosis In Vivo and In Vitro
  • BI 685509 Reduces Portal Hypertension in TAA Cirrhosis Model
Show more Gastrointestinal, Hepatic, Pulmonary, and Renal

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics