Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleBehavioral Pharmacology

Sialorphin Potentiates Effects of [Met5]Enkephalin without Toxicity by Action other than Peptidase Inhibition

Takugi Kan, Masanobu Yoshikawa, Mariko Watanabe, Masaaki Miura, Kenji Ito, Mitsumasa Matsuda, Kayoko Iwao, Hiroyuki Kobayashi, Takeshi Suzuki and Toshiyasu Suzuki
Journal of Pharmacology and Experimental Therapeutics October 2020, 375 (1) 104-114; DOI: https://doi.org/10.1124/jpet.120.266080
Takugi Kan
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masanobu Yoshikawa
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mariko Watanabe
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masaaki Miura
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Ito
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitsumasa Matsuda
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kayoko Iwao
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Kobayashi
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeshi Suzuki
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toshiyasu Suzuki
Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
  • 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

This dose-response study investigated the effects of sialorphin on [Met5]enkephalin (ME)-induced inhibition of contractions in mouse vas deferens and antinociception in male rats. Differences were compared among combinations of three chemical peptidase inhibitors: amastatin, captopril, and phosphoramidon. The ratio of potencies of ME in mouse vas deferens pretreated with both sialorphin (100 µM) and a mixture of the three peptidase inhibitors (1 µM each) was higher than that with the mixture of peptidase inhibitors alone at any dose. Intrathecal administration of sialorphin (100–400 nmol) significantly and dose dependently increased ME (3 nmol)-induced antinociception with the mixture of three peptidase inhibitors (10 nmol each). The degree of antinociception with a combination of any two of the peptidase inhibitors (10 nmol each) in the absence of sialorphin was less than that in the presence of sialorphin (200 nmol). Pretreatment with both sialorphin (200 nmol) and the mixture of three peptidase inhibitors (10 nmol each) produced an approximately 100-fold augmentation in ME (10 nmol)-induced antinociception, but without signs of toxicity such as motor dysfunction in rats. Radioligand receptor binding assay revealed that sialorphin did not affect either binding affinity or maximal binding capacity of [d-Ala2,N-MePhe4,Gly-ol5]enkephalin. These results indicate that sialorphin potentiates the effects of ME without toxicity by a mechanism other than peptidase inhibition and with no effect on its affinity to µ-opioid receptors.

SIGNIFICANCE STATEMENT Sialorphin is regarded as an endogenous peptidase inhibitor that interacts with enkephalin-degrading enzymes. The results of these in vitro and in vivo studies confirm that sialorphin potentiates the effects of [Met5]enkephalin without toxicity by an action other than peptidase inhibition. This suggests that sialorphin offers the advantage of reducing or negating the side effects of opioid drugs and endogenous opioid peptides.

Footnotes

    • Received March 2, 2020.
    • Accepted July 28, 2020.
  • This work was partially supported by grants from 2020 Tokai University School of Medicine Research Aid and JSPS (Japan Society for the Promotion of Science) KAKENHI: Grant [18K0886], [18K08830], and [18K08831].

  • The authors declare no conflict of interest.

  • https://doi.org/10.1124/jpet.120.266080.

  • Copyright © 2020 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: 375 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 375, Issue 1
1 Oct 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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.
Sialorphin Potentiates Effects of [Met5]Enkephalin without Toxicity by Action other than Peptidase Inhibition
(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 ArticleBehavioral Pharmacology

Sialorphin Potentiates Effects of [Met5]Enkephalin

Takugi Kan, Masanobu Yoshikawa, Mariko Watanabe, Masaaki Miura, Kenji Ito, Mitsumasa Matsuda, Kayoko Iwao, Hiroyuki Kobayashi, Takeshi Suzuki and Toshiyasu Suzuki
Journal of Pharmacology and Experimental Therapeutics October 1, 2020, 375 (1) 104-114; DOI: https://doi.org/10.1124/jpet.120.266080

Citation Manager Formats

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

Sialorphin Potentiates Effects of [Met5]Enkephalin

Takugi Kan, Masanobu Yoshikawa, Mariko Watanabe, Masaaki Miura, Kenji Ito, Mitsumasa Matsuda, Kayoko Iwao, Hiroyuki Kobayashi, Takeshi Suzuki and Toshiyasu Suzuki
Journal of Pharmacology and Experimental Therapeutics October 1, 2020, 375 (1) 104-114; DOI: https://doi.org/10.1124/jpet.120.266080
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Varenicline and epibatidine as opioid adjuvants
  • MCAM reverses and prevents fentanyl ventilatory depression
  • Kv7 opener SCR2682 alleviates pain
Show more Behavioral Pharmacology

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics