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

Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Secretoneurin Release and Secretogranin II Gene Transcription in Bovine Adrenochromaffin Cells through Multiple Signaling Pathways and Increased Binding of Pre-Existing Activator Protein-1-Like Transcription Factors

Valerie Turquier, Laurent Yon, Luca Grumolato, David Alexandre, Alain Fournier, Hubert Vaudry and Youssef Anouar
Molecular Pharmacology July 2001, 60 (1) 42-52; DOI: https://doi.org/10.1124/mol.60.1.42
Valerie Turquier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent Yon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luca Grumolato
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Alexandre
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alain Fournier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hubert Vaudry
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Youssef Anouar
  • 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

Secretoneurin (SN) is a novel bioactive peptide that derives from the neuroendocrine protein secretogranin II (SgII) by proteolytic processing and participates in neuro-immune communication. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP-38) dose-dependently stimulates (EC50 ∼ 3 nM) SN release (up to 4-fold) and SgII gene expression (up to 60-fold) in cultured bovine adrenochromaffin cells. The effect of PACAP on both SN secretion and SgII mRNA levels is rapid and long lasting. We analyzed in this neuroendocrine cell model the transduction pathways involved in both SN secretion and SgII gene transcription in response to PACAP. The cytosolic calcium chelator BAPTA-AM and the nonselective calcium channel antagonist NiCl2 equally inhibited both secretion of the peptide and transcription of the SgII gene, indicating a major contribution of calcium influx in PACAP-induced SN biosynthesis and release in chromaffin cells. Inhibition of protein kinase A (PKA) or C (PKC) also reduced PACAP-evoked SN release but did not alter the stimulatory effect of PACAP on SgII mRNA levels. Conversely, application of mitogen-activated protein kinase inhibitors suppressed PACAP-induced SgII gene expression. The effect of PACAP on SgII mRNA levels, like the effect of the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate (TPA), was not affected by cycloheximide, whereas the effects of the PKA stimulator forskolin or cell-depolarization by high K+ were significantly reduced by the protein synthesis inhibitor. PACAP and TPA both increased the binding activity of the SgII cAMP response element to trans-acting factors present in chromaffin cell nuclear extracts, which are recognized by antibodies to activator protein-1-related proteins. These data indicate that SN biosynthesis is regulated by PACAP in chromaffin cells through complex signaling cascades, suggesting that SN may play a function duringtrans-synaptic stimulation of the adrenal medulla.

  • Abbreviations

    SN
    secretoneurin
    SgII
    secretogranin II
    CgA
    chromogranin A
    PACAP
    pituitary adenylate cyclase-activating polypeptide
    PAC1-R
    pituitary adenylate cyclase-activating polypeptide-preferring receptor
    VIP
    vasoactive intestinal polypeptide
    MAPK
    mitogen-activated protein kinase
    PKC
    protein kinase C
    PKA
    protein kinase A
    AP-1
    activator protein-1
    TPA
    12-O-tetradecanoylphorbol 13-acetate
    BAPTA
    1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid
    AM
    acetoxymethyl ester
    RIA
    radioimmunoassay
    ERK
    extracellular signal-regulated kinase
    EMSA
    electrophoretic mobility shift assay
    VOCCs
    voltage-operated calcium channels
    ATF
    activating transcription factors
    CRE
    cAMP response element
    CREB
    cAMP response element binding protein
    • Received September 9, 2000.
    • Accepted January 29, 2001.
    • 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: 60 (1)
    Molecular Pharmacology
    Vol. 60, Issue 1
    1 Jul 2001
    • Table of Contents
    • About the Cover
    • Index by author
    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.
    Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Secretoneurin Release and Secretogranin II Gene Transcription in Bovine Adrenochromaffin Cells through Multiple Signaling Pathways and Increased Binding of Pre-Existing Activator Protein-1-Lik…
    (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

    Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Secretoneurin Release and Secretogranin II Gene Transcription in Bovine Adrenochromaffin Cells through Multiple Signaling Pathways and Increased Binding of Pre-Existing Activator Protein-1-Like Transcription Factors

    Valerie Turquier, Laurent Yon, Luca Grumolato, David Alexandre, Alain Fournier, Hubert Vaudry and Youssef Anouar
    Molecular Pharmacology July 1, 2001, 60 (1) 42-52; DOI: https://doi.org/10.1124/mol.60.1.42

    Citation Manager Formats

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

    Share
    Research ArticleArticle

    Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Secretoneurin Release and Secretogranin II Gene Transcription in Bovine Adrenochromaffin Cells through Multiple Signaling Pathways and Increased Binding of Pre-Existing Activator Protein-1-Like Transcription Factors

    Valerie Turquier, Laurent Yon, Luca Grumolato, David Alexandre, Alain Fournier, Hubert Vaudry and Youssef Anouar
    Molecular Pharmacology July 1, 2001, 60 (1) 42-52; DOI: https://doi.org/10.1124/mol.60.1.42
    del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Jump to section

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

    Related Articles

    Cited By...

    More in this TOC Section

    • The binding site for KCI807 in the androgen receptor
    • Fatty acid amide hydrolase in cisplatin nephrotoxicity
    • eCB Signaling System in hiPSC-Derived Neuronal Cultures
    Show more Article

    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