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

Somatostatin Increases Phospholipase D Activity and Phosphatidylinositol 4,5-bisphosphate Synthesis in Clonal β Cells HIT-T15

Henrique Cheng, Justin A. Grodnitzky, Sirintorn Yibchok-anun, Jing Ding and Walter H. Hsu
Molecular Pharmacology June 2005, 67 (6) 2162-2172; DOI: https://doi.org/10.1124/mol.104.010470
Henrique Cheng
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Justin A. Grodnitzky
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sirintorn Yibchok-anun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Ding
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Walter H. Hsu
  • 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

In the presence of arginine vasopressin (AVP), somatostatin increases [Ca2+]i, leading to a transient increase in insulin release from clonal β cells HIT-T15 via Gi/o and phospholipase C (PLC) pathway (Cheng et al., 2002a). The present study was to elucidate the mechanisms underlying somatostatin-induced [Ca2+]i increase in the presence of AVP. We found that the effect of somatostatin was mediated by βγ subunits but not by the α subunit of Gi/o. Because somatostatin alone failed to increase [Ca2+]i, we hypothesized that somatostatin increases phosphatidylinositol 4,5-bisphosphate (PIP2) synthesis, providing extra substrate for preactivated PLC-β to generate inositol 1,4,5-trisphosphate (IP3). Somatostatin alone did not increase IP3 levels, but AVP + somatostatin did. Somatostatin increased PIP2 levels but decreased phosphatidylinositol 4-phosphate levels. We further hypothesized that PLD mediates somatostatin-induced changes in PIP2 levels. Both the phospholipase D (PLD) inhibitors and antibody versus PLD1 antagonized AVP-somatostatin-induced increases in [Ca2+]i. PLD inhibitor also antagonized somatostatin-induced increase in PIP2 levels. In addition, somatostatin increased PLD activity. These results suggest that activation of somatostatin receptors that are coupled to the βγ dimer of Gi/o led to PLD1 activation, thus promoting the synthesis of phosphatidic acid. Phosphatidic acid activates PIP-5 kinase, which evokes an increase in PIP2 synthesis. The PIP2 generated by somatostatin administration increases substrate for preactivated phospholipase C-β, which hydrolyzes PIP2 to form IP3, leading to an increase in [Ca2+]i. The regulation of PIP2 synthesis by Gi/o-coupled receptors via PLD activation represents a novel signaling mechanism for somatostatin and a novel concept in the cross-talk between Gq- and Gi/o-coupled receptors in β cells.

  • Received December 19, 2004.
  • Accepted March 22, 2005.
  • 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: 67 (6)
Molecular Pharmacology
Vol. 67, Issue 6
1 Jun 2005
  • 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.
Somatostatin Increases Phospholipase D Activity and Phosphatidylinositol 4,5-bisphosphate Synthesis in Clonal β Cells HIT-T15
(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

Somatostatin Increases Phospholipase D Activity and Phosphatidylinositol 4,5-bisphosphate Synthesis in Clonal β Cells HIT-T15

Henrique Cheng, Justin A. Grodnitzky, Sirintorn Yibchok-anun, Jing Ding and Walter H. Hsu
Molecular Pharmacology June 1, 2005, 67 (6) 2162-2172; DOI: https://doi.org/10.1124/mol.104.010470

Citation Manager Formats

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

Share
Research ArticleArticle

Somatostatin Increases Phospholipase D Activity and Phosphatidylinositol 4,5-bisphosphate Synthesis in Clonal β Cells HIT-T15

Henrique Cheng, Justin A. Grodnitzky, Sirintorn Yibchok-anun, Jing Ding and Walter H. Hsu
Molecular Pharmacology June 1, 2005, 67 (6) 2162-2172; DOI: https://doi.org/10.1124/mol.104.010470
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 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