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

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Valerie B. Caraiscos, Robert P. Bonin, J. Glen Newell, Elzbieta Czerwinska, John F. Macdonald and Beverley A. Orser
Molecular Pharmacology May 2007, 71 (5) 1277-1287; DOI: https://doi.org/10.1124/mol.106.033563
Valerie B. Caraiscos
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert P. Bonin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Glen Newell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elzbieta Czerwinska
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John F. Macdonald
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Beverley A. Orser
  • 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 mechanisms by which insulin modulates neuronal plasticity and pain processes remain poorly understood. Here we report that insulin rapidly increases the function of glycine receptors in murine spinal neurons and recombinant human glycine receptors expressed in human embryonic kidney cells. Whole-cell patch-clamp recordings showed that insulin reversibly enhanced current evoked by exogenous glycine and increased the amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents recorded in cultured spinal neurons. Insulin (1 μM) also shifted the glycine concentration-response plot to the left and reduced the glycine EC50 value from 52 to 31 μM. Currents evoked by a submaximal concentration of glycine were increased to approximately 140% of control. The glycine receptor α subunit was sufficient for the enhancement by insulin because currents from recombinant homomeric α1 receptors and heteromeric α1β receptors were both increased. Insulin acted at the insulin receptor via pathways dependent on tyrosine kinase and phosphatidylinositol 3 kinase because the insulin effect was eliminated by the insulin receptor antagonist, hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol 3 kinase antagonist wortmannin. Together, these results show that insulin has a novel regulatory action on the potency of glycine for ionotropic glycine receptors.

Footnotes

  • This research is supported by operating grants from the Canadian Institutes of Health Research (to B.A.O.) (MOP-38028), a Career Scientist Award (to B.A.O.), a Canadian Institutes of Health Research doctoral research award (to V.B.C.) (56381) and postdoctoral fellowship award (to J.G.N.) (63508). B.A.O. is a Canada Research Chair in Anesthesia.

  • B.A.O. serves as a scientific advisor to Merck Sharp and Dohme Inc.

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

  • doi:10.1124/mol.106.033563.

  • ABBREVIATIONS: GlyR, glycine receptor; GABAA, γ-aminobutyric acid subtype A; PKC, protein kinase C; PI3, phosphatidylinositol 3; MEM, minimum essential medium; FBS, fetal bovine serum; DIV, days in vitro; HEK, human embryonic kidney; mIPSC, miniature inhibitory postsynaptic current; HNMPA, hydroxyl-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester; DMSO, dimethyl sulfoxide; PBS, phosphate-buffered saline; IGly, glycine current; NMDA, N-methyl-d-aspartate; IGF, insulin-like growth factor.

    • Received December 22, 2006.
    • Accepted February 15, 2007.
  • 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: 71 (5)
Molecular Pharmacology
Vol. 71, Issue 5
1 May 2007
  • 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.
Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors
(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

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Valerie B. Caraiscos, Robert P. Bonin, J. Glen Newell, Elzbieta Czerwinska, John F. Macdonald and Beverley A. Orser
Molecular Pharmacology May 1, 2007, 71 (5) 1277-1287; DOI: https://doi.org/10.1124/mol.106.033563

Citation Manager Formats

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

Share
Research ArticleArticle

Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors

Valerie B. Caraiscos, Robert P. Bonin, J. Glen Newell, Elzbieta Czerwinska, John F. Macdonald and Beverley A. Orser
Molecular Pharmacology May 1, 2007, 71 (5) 1277-1287; DOI: https://doi.org/10.1124/mol.106.033563
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
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Effects of Small Molecule Ligands on ACKR3 Receptors
  • Michaelis-Menten Quantification of GPCR-G Protein Signaling
  • Anti-aromatase activity of exemestane phase II metabolites
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics