Skip Navigation

Cardiovascular Research 2003 60(3):529-537; doi:10.1016/j.cardiores.2003.09.012
© 2003 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Neumann, J.
Right arrow Articles by Schmitz, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Neumann, J.
Right arrow Articles by Schmitz, W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2003, European Society of Cardiology

Altered signal transduction in cardiac ventricle overexpressing A1-adenosine receptors

Joachim Neumanna, Peter Boknik*,a, Frank Begrowa, Gabriela Hanskea, Isabel Justusa, Marek Mat'usa, Uta Reinkea, G.Paul Matherneb and Wilhelm Schmitza

aInstitut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Domagkstraße 12, D-48129 Münster, Germany
bDepartment of Pediatrics, University of Virginia, Charlottesville, VA, USA

*Corresponding author. Tel.: +49-251-8355510; fax: +49-251-8355501. Email address: boknik{at}uni-muenster.de

Objective: The aim of the present study was to assess the effects of A1-adenosine receptor (A1-AR) stimulation in ventricle of A1-adenosine receptor overexpressing mice (transgenic mice, TG). Methods: Effects of the A1-adenosine receptor agonist R-PIA ((–)-N6-phenylisopropyladenosine) on phosphorylation of phospholamban (PLB), Ca2+ transients, Ca2+ currents and cell shortening were studied in isolated ventricular cardiomyocytes. Results: R-PIA alone did not affect contractility in isolated electrically stimulated cardiomyocytes from wild-type mice (WT) or TG. However, after pre-stimulation of β-adrenoceptors by isoproterenol, R-PIA reduced contractility in cardiomyocytes from WT but increased contractility in TG. Under the same conditions, R-PIA reduced isoproterenol-stimulated currents through L-type Ca2+ channels, Ca2+ transients and phosphorylation of PLB in cardiomyocytes from WT. In contrast, R-PIA diminished phospholamban phosphorylation induced by isoproterenol but augmented isoproterenol-elevated currents through L-type Ca2+ channels, and isoproterenol-heightened Ca2+ transients in cardiomyocytes from TG. Conclusions: We suggest that A1-adenosine receptor overexpression reverses the interaction of β-adrenergic and A1-adenosine receptor stimulation, at least in part. Hence, the receptor/effector coupling is dependent on receptor density in this model.

KEYWORDS Adenosine; Blood pressure; Ca-channel; Contractile function; Protein phosphorylation

Time for primary review 31 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.