Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca(2+)-dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange.
K Nagai, … , T Tomita, S Sasayama
K Nagai, … , T Tomita, S Sasayama
Published January 1, 1996
Citation Information: J Clin Invest. 1996;97(1):6-13. https://doi.org/10.1172/JCI118407.
View: Text | PDF
Research Article

Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca(2+)-dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange.

  • Text
  • PDF
Abstract

Whereas mobilization of intracellular Ca2+ stimulates neuronal adenylyl cyclase via Ca2+/calmodulin, mobilized Ca2+ directly inhibits adenylyl cyclase in other tissues. To determine the physiologic role of the Ca(2+)-dependent interaction between Na+/Ca2+ exchange and beta-adrenergic signal transduction in the intact heart, digoxin (0.3 mg/kg) was administered intravenously in rabbits. 30 min after the administration, digoxin impaired the peak left ventricular dP/dt response to dobutamine infusions by up to 38% as compared with control rabbits. This impairment was not caused by changes in either beta-adrenergic receptor number or in the functional activity of stimulatory guanine nucleotide-binding protein. It was associated with 33-36% reductions in basal and stimulated adenylyl cyclase activities. Animals treated with calcium gluconate (20 mg/kg/min for 30 min) also demonstrated similar reductions in adenylyl cyclase activities. In addition, increasing the free Ca2+ concentration progressively inhibited adenylyl cyclase activity in the control, digoxin-treated, and calcium gluconate-treated sarcolemma preparations in vitro. Moreover, digoxin and calcium gluconate pretreatment blunted the increase in cAMP in myocardial tissue after dobutamine infusion in vivo. Thus, digoxin rapidly reduces beta-adrenergic contractile response in rabbit hearts. This reduction may reflect an inhibition of adenylyl cyclase by Ca2+ mobilized via Na+/Ca2+ exchange.

Authors

K Nagai, T Murakami, T Iwase, T Tomita, S Sasayama

×

Total citations by year

Year: 2011 2006 2002 2001 1998 Total
Citations: 1 1 2 1 2 7
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (7)

Title and authors Publication Year
Fetal and Neonatal Physiology
LH Johnson, VK Bhutani
Fetal and Neonatal Physiology 2011
Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy
GD Mills, H Kubo, DM Harris, RM Berretta, V Piacentino, SR Houser
American journal of physiology. Heart and circulatory physiology 2006
Digoxin- and Monensin-induced Changes of Intracellular Ca2+ Concentration in Isolated Guinea-pig Ventricular Myocyte
I Meral, W Hsu, FB Hembrough
Journal of Veterinary Medicine Series A 2002
Calcium Cycling, Historic Overview and Perspectives. Role for Autonomic Nervous System Regulation
NN Petrashevskaya, SE Koch, I Bodi, A Schwartz
Journal of Molecular and Cellular Cardiology 2002
Inhibition of Phosphodiesterase Type III Before Aortic Cross-Clamping Preserves Intramyocardial Cyclic Adenosine Monophosphate During Cardiopulmonary Bypass
GM Janelle, F Urdaneta, ML Blas, J Shryock, YS Tang, TD Martin, EB Lobato
Anesthesia and Analgesia 2001
Effect of ventricular stretch on contractile strength, calcium transient, and cAMP in intact canine hearts
K Todaka, K Ogino, A Gu, D Burkhoff
American journal of physiology. Heart and circulatory physiology 1998
Effect of Digoxin on Ventricular Remodeling and Responsiveness of β-Adrenoceptors in Chronic Volume Overload
JT Sullebarger, PM D'Ambra, LC Clark, L Thanikarry, HL Fontanet
Journal of cardiovascular pharmacology and therapeutics 1998

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts