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

In Vivo Signal Transduction of Nociceptive Response by Kyotorphin (Tyrosine-Arginine) through Gαi- and Inositol Trisphosphate-Mediated Ca2+ Influx

Hiroshi Ueda and Makoto Inoue
Molecular Pharmacology January 2000, 57 (1) 108-115;
Hiroshi Ueda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Makoto Inoue
  • 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

Kyotorphin is a dipeptidic neuropeptide (tyrosine-arginine) that has specific receptor coupled to Gi and phospholipase C and elicits Met-enkephalin release. Here, we attempted to demonstrate the in vivo evidence for the presynaptic mechanism by analyzing its nociceptive responses after peripheral application. Kyotorphin elicited potent nociceptive flexor responses at extremely low doses between 0.1 and 100 fmol after the intraplantar injection into the hind-limb of mice. The site of action of kyotorphin-induced responses was identified to be on nociceptor endings, because the responses were markedly attenuated by intrathecal pretreatments with Gαi1 or Gαi2 antisense-oligodeoxynucleotides. Similar mechanisms were observed with histamine-induced nociceptive responses, except for the use of different antagonist and Gαq/11antisense-oligodeoxynucleotide. Both responses were characterized to be mediated through inositol trisphosphate receptor-gated Ca2+influx, because they were blocked by xestospongin C, an allosteric antagonist for inositol trisphosphate receptor and EGTA, but not thapsigargin. Because the nociceptive responses by compound 48/80 through histamine-release from mast cells were completely abolished by thapsigargin, it is unlikely that the dose of thapsigargin is not sufficient to block both responses. All of these in vivo findings strongly support our previous view that kyotorphin elicits Ca2+ influx through inositol trisphosphate receptor located at presynaptic plasma membranes.

Footnotes

  • Send reprint requests to: Dr. Hiroshi Ueda, Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, 1–14 Bunkyo-machi, Nagasaki 852-8521, Japan. E-mail: ueda{at}net.nagasaki-u.ac.jp

  • This work was supported in part by grants-in-aid from the Ministry of Education, Science, Culture and Sports of Japan and by grants from The Naito Foundation.

  • Abbreviations:
    Kyo
    kyotorphin
    AS-ODN
    antisense oligodeoxynucleotide
    MS-ODN
    missense oligodeoxynucleotide
    PLC
    phospholipase C
    InsP3
    inositol 1,4,5-trisphosphate
    DRG
    dorsal root ganglions
    PTX
    pertussis toxin
    ChTX
    cholera toxin
    BK
    bradykinin
    SP
    substance P
    DPH
    diphenhydramine hydrochloride
    i.pl.
    intraplantarly
    i.t.
    intrathecal
    • Received April 23, 1999.
    • Accepted October 13, 1999.
  • 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: 57 (1)
Molecular Pharmacology
Vol. 57, Issue 1
1 Jan 2000
  • 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.
In Vivo Signal Transduction of Nociceptive Response by Kyotorphin (Tyrosine-Arginine) through Gαi- and Inositol Trisphosphate-Mediated Ca2+ Influx
(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

In Vivo Signal Transduction of Nociceptive Response by Kyotorphin (Tyrosine-Arginine) through Gαi- and Inositol Trisphosphate-Mediated Ca2+ Influx

Hiroshi Ueda and Makoto Inoue
Molecular Pharmacology January 1, 2000, 57 (1) 108-115;

Citation Manager Formats

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

Share
Research ArticleArticle

In Vivo Signal Transduction of Nociceptive Response by Kyotorphin (Tyrosine-Arginine) through Gαi- and Inositol Trisphosphate-Mediated Ca2+ Influx

Hiroshi Ueda and Makoto Inoue
Molecular Pharmacology January 1, 2000, 57 (1) 108-115;
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Polypharmacology of CBL0137 in the African Trypanosome
  • Peptide-mediated differential signaling at GPR83
  • Therapeutic Effects of FGF23 Antagonists in Hyp Mice
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics