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
OtherRENAL PHARMACOLOGY

Guanine Nucleotide-Binding Inhibitory Protein-Mediated Inhibition of Adenylyl Cyclase Is Enhanced in Spontaneously Hypertensive Rat Preglomerular Arteriolar Smooth Muscle Cells

Subhash J. Vyas, Rupa Mokkapatti, Raghvendra K. Dubey, Mala R. Chinoy and Edwin K. Jackson
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 828-834;
Subhash J. Vyas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rupa Mokkapatti
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raghvendra K. Dubey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mala R. Chinoy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edwin K. Jackson
  • 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 purpose of our study was to determine whether Gi-mediated control over adenylyl cyclase in preglomerular arteriolar smooth muscle cells (PGASMC) is enhanced in the spontaneously hypertensive rat (SHR). PGASMC were cultured from preglomerular microvessels isolated from adult SHR (14-15 wk of age) and age-matched WKY rats. Confluent monolayers of cells in third passage were used for the experiments. cAMP released into the media (30 min) as well as cellular levels of cAMP were measured in the presence of a phosphodiesterase inhibitor, 1-isobutyl-3-methyl-xanthine (IBMX; 100 μM) and expressed as pmol/mg protein. Total (released + cellular) cAMP was significantly lower in SHR (14.19 ± 2.30 pmol/mg protein) as compared with WKY (28.3 ± 3.04 pmol/mg protein). Correspondingly, the released (4.6 ± 0.4 pmol/mg protein) as well as cellular (9.78 ± 2.18 pmol/mg protein) cAMP levels were also significantly lower in SHR when compared with WKY (8.85 ± 1.26 and 18.86 ± 2.0 pmol/mg protein, respectively). The steady-state levels of none of the Giα subunits, namely Giα1, Giα2 and Giα3, were higher in the SHR PGASMC. Pertussis toxin treatment (PTX; 100 ng/ml; 24 hr) caused complete ADP-ribosylation of Giα subunits in both WKY and SHR PGASMC. The same treatment of PTX also produced a significant increase in total cAMP in SHR, but not in WKY, such that the total cAMP levels after PTX treatment were not significantly different between the two strains. Interestingly, PTX significantly increased the released (20.26 ± 0.90 pmol/mg protein) but not the cellular (13.63 ± 1.63 pmol/mg protein) cAMP in SHR. Forskolin (1 μM) induced similar increases in total cAMP and isoproterenol (1 μM) caused greater increases in total cAMP in SHR cells compared with WKY cells. These data strongly suggest that in SHR PGASMC total adenylyl cyclase activity is not altered. Furthermore, steady-state expressions of G iα-1, Giα-2 and Giα-3 are not increased whereas Gi -mediated inhibition of adenylyl cyclase is augmented in SHR PGASMC.

Footnotes

  • Send reprint requests to: Dr. Subhash J. Vyas, Center for Clinical Pharmacology, Scaife Hall, Room 623, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213-2582.

  • ↵1 This work was supported by Grants HL-35909 and HL-55314 from the National Institutes of Health Bethesda, MD. A portion of this work was presented at the Experimental Biology, 1996 Annual Meeting, Washington, D.C., April 14-17 and was published as an abstract (FASEB J10:A698, 1996).

  • Abbreviations:
    SHR
    spontaneously hypertensive rat
    WKY
    Wistar-Kyoto
    cAMP
    adenosine 3′, 5′-cyclic monophosphate
    Ang II
    angiotensin II
    ISO
    isoproterenol
    Gi, guanine nucleotide-binding inhibitory protein
    Gs,guanine nucleotide-binding stimulatory protein
    IBMX
    3-isobutyl-1-methyl-xanthine
    PTX
    pertussis toxin
    PGASMC
    preglomerular arteriolar smooth muscle cells
    DMEM
    Dulbecco’s modified Eagle medium
    PBS
    phosphate-buffered saline
    • Received March 28, 1997.
    • Accepted January 20, 1998.
  • 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. 285, Issue 2
1 May 1998
  • 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.
Guanine Nucleotide-Binding Inhibitory Protein-Mediated Inhibition of Adenylyl Cyclase Is Enhanced in Spontaneously Hypertensive Rat Preglomerular Arteriolar Smooth Muscle Cells
(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
OtherRENAL PHARMACOLOGY

Guanine Nucleotide-Binding Inhibitory Protein-Mediated Inhibition of Adenylyl Cyclase Is Enhanced in Spontaneously Hypertensive Rat Preglomerular Arteriolar Smooth Muscle Cells

Subhash J. Vyas, Rupa Mokkapatti, Raghvendra K. Dubey, Mala R. Chinoy and Edwin K. Jackson
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 828-834;

Citation Manager Formats

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

Guanine Nucleotide-Binding Inhibitory Protein-Mediated Inhibition of Adenylyl Cyclase Is Enhanced in Spontaneously Hypertensive Rat Preglomerular Arteriolar Smooth Muscle Cells

Subhash J. Vyas, Rupa Mokkapatti, Raghvendra K. Dubey, Mala R. Chinoy and Edwin K. Jackson
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 828-834;
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
    • Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Regulation of Renin Secretion Through Reversible Phosphorylation of Myosin by Myosin Light Chain Kinase and Protein Phosphatase Type 1
  • Interaction of l-Arginine Analogs withl-Arginine Uptake in Rat Renal Brush Border Membrane Vesicles
  • Effects of Trimetazidine on Lipid Peroxidation and Phosphorus Metabolites during Cold Storage and Reperfusion of Isolated Perfused Rat Kidneys
Show more RENAL 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