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
  • Log out
  • 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
  • Log out
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherCARDIOVASCULAR PHARMACOLOGY

Effect of Tachykinin Receptor Inhibition in the Brain on Cardiovascular and Behavioral Responses to Stress

Juraj Culman, Sabine Klee, Christina Ohlendorf and Thomas Unger
Journal of Pharmacology and Experimental Therapeutics January 1997, 280 (1) 238-246;
Juraj Culman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sabine Klee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christina Ohlendorf
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Unger
  • 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 neurokinins, substance P (SP) and neurokinin A (NKA) represent natural, nonspecific ligands of NK1 and NK2receptors. In our study in conscious rats, we tested the hypothesis that neurokinins, especially SP, are used by neuronal circuits to generate cardiovascular and behavioral responses to stress by using the selective, high-affinity, nonpeptide antagonists of NK1 and NK2 receptors, CP-96, 345, RP 67580 and SR 48968, respectively, Formalin injected s.c. through a chronically implanted catheter in the region of the lower leg was used as a stress stimulus. The antagonists and their inactive enantiomers, RP 68651 and SR 48965, as a control for nonspecific activity, were injected intracerebroventricularly (i.c.v.) 10 min before the s.c. injection of formalin. Formalin (2.5%, 50 μl, s.c.) induced a marked increase in mean arterial pressure (MAP) and heart rate (HR) as well as hind limb grooming/biting (HG) as the dominant behavioral manifestation. Pretreatment with the NK1 receptor antagonist, CP-96,345 (5 nmol, i.c.v.), significantly attenuated only the HR (-54%; P < .01) but not the MAP response to formalin. The NK1 receptor antagonist, RP 67580, injected i.c.v. at doses of 100, 500 and 2500 pmol significantly reduced both, the MAP and HR responses to formalin by maximally 63% (P < .01) and 52% (P < .01), respectively. In a separate set of experiments, we compared the effect of the individual and simultaneous blockade of central NK1and NK2 receptors on the cardiovascular and behavioral responses to formalin stress. Pretreatment with RP 67580 (100 pmol, i.c.v.) attenuated the MAP (-30%; P < .05), HR (-40%; P < .01) and HG (P < .05) responses to formalin. The NK2receptor antagonist, SR 48968 (650 pmol, i.c.v.), affected neither the cardiovascular nor the behavioral responses. I.c.v. pretreatment with both tachykinin receptor antagonists (RP 67580: 100 pmol; SR 48968: 650 pmol) reduced the MAP, HR and HG responses to formalin to the same extent as RP 67580 alone. Pretreatment with the inactive enantiomers, RP 68651 (100 pmol, i.c.v.) and SR 48965 (650 pmol, i.c.v.) did not alter the cardiovascular and behavioral responses to formalin. Our results demonstrate that centrally administered NK1receptor antagonists inhibit the cardiovascular and behavioral reactions in response to a noxious stimulus. They provide first pharmacological evidence that endogenous SP acts as mediator of stress responses in the brain.

Footnotes

  • Send reprint requests to: Dr. Juraj Culman, Department of Pharmacology, Christian-Albrechts-University of Kiel, Hospitalstrasse 4, 24105 Kiel, Germany.

  • Abbreviations:
    AUC
    area under the curve
    BP
    blood pressure
    DMN
    dorsomedial nucleus
    FW
    face washing/head scratching
    HG
    hind limb grooming/biting
    HR
    heart rate
    i.c.v.
    intracerebroventricular(ly)
    MAP
    mean arterial pressure
    NKA
    neurokinin A
    NKB
    neurokinin B
    PAG
    periaqueductal gray
    PVN
    paraventricular nucleus
    SP
    substance P
    VMN
    ventromedial nucleus
    WDS
    wet dog shakes
    ANOVA
    analysis of variance
    • Received November 27, 1995.
    • Accepted September 16, 1996.
  • 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
Vol. 280, Issue 1
1 Jan 1997
  • Table of Contents
  • Index by author
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.
Effect of Tachykinin Receptor Inhibition in the Brain on Cardiovascular and Behavioral Responses to Stress
(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
OtherCARDIOVASCULAR PHARMACOLOGY

Effect of Tachykinin Receptor Inhibition in the Brain on Cardiovascular and Behavioral Responses to Stress

Juraj Culman, Sabine Klee, Christina Ohlendorf and Thomas Unger
Journal of Pharmacology and Experimental Therapeutics January 1, 1997, 280 (1) 238-246;

Citation Manager Formats

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

Share
OtherCARDIOVASCULAR PHARMACOLOGY

Effect of Tachykinin Receptor Inhibition in the Brain on Cardiovascular and Behavioral Responses to Stress

Juraj Culman, Sabine Klee, Christina Ohlendorf and Thomas Unger
Journal of Pharmacology and Experimental Therapeutics January 1, 1997, 280 (1) 238-246;
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
    • Methods
    • Materials
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • TAS-301, an Inhibitor of Smooth Muscle Cell Migration and Proliferation, Inhibits Intimal Thickening after Balloon Injury to Rat Carotid Arteries
  • Identification of Low Molecular Weight GP IIb/IIIa Antagonists That Bind Preferentially to Activated Platelets
  • Differential Contribution of Angiotensinergic and Cholinergic Receptors in the Hypothalamic Paraventricular Nucleus to Osmotically Induced AVP Release
Show more CARDIOVASCULAR PHARMACOLOGY

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 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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics