JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
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 Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thomas, G. P.
Right arrow Articles by Karmazyn, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, G. P.
Right arrow Articles by Karmazyn, M.

Vol. 286, Issue 3, 1208-1214, September 1998

Hydrogen Peroxide-Induced Stimulation of L-Type Calcium Current in Guinea Pig Ventricular Myocytes and Its Inhibition by Adenosine A1 Receptor Activation1

George P. Thomas2, Stephen M. Sims, Michael A. Cook and Morris Karmazyn

Department of Pharmacology & Toxicology and Physiology, Medical Sciences Building, The University of Western Ontario, London, Ontario, Canada N6A 5C1

Hydrogen peroxide (H2O2) produces complex cardiac effects that may involve altered calcium homeostasis. The cardiotoxic effects of H2O2 can be attenuated by adenosine A1 receptor agonists. The present study examined the effect of H2O2 on L-type Ca++ current (ICa,L) in guinea pig ventricular myocytes under two different recording conditions and the influence of adenosine receptor agonists. H2O2 (100 µM), did not have any significant effect on ICa,L, under conventional whole cell patch configuration. However, when recorded under nystatin perforated patch configuration, H2O2 caused a gradual and significant increase (84 ± 14%) in ICa,L compared to control values. N6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, significantly attenuated the effect of H2O2. The inhibitory effect of N6-cyclopentyladenosine was antagonized by 8cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor antagonist. The A2A and A3 receptor agonists, 2-p-(2-Carboxyethyl)phenethylamino-5'- N - ethylcarboxamidoadenosine (CGS-21680) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-beta -D-ribofuranuronamide, respectively, did not modulate the enhancement of ICa,L by H2O2. Moreover the effects of N6-cyclopentyladenosine were mimicked by the protein kinase C inhibitor bisindolylmaleimide. Thus, our results demonstrate a potent stimulatory effect of H2O2 on ICa,L in guinea pig ventricular myocytes. We further demonstrate that adenosine A1 receptor activation attenuates this effect. Our results suggest a potential basis for altered calcium homeostasis in response to H2O2 as well as the salutary effects of A1 receptor activation against H2O2-induced cardiotoxicity.

0022-3565/98/2863-1208$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Card Surg AdultHome page
R. M. Mentzer Jr, M. S. Jahania, and R. D. Lasley
Myocardial Protection
Card. Surg. Adult, January 1, 2008; 3(2008): 443 - 464.
[Full Text]

Home page
 J. Biol. Chem.Home page
J. P. Brennan, S. C. Bardswell, J. R. Burgoyne, W. Fuller, E. Schroder, R. Wait, S. Begum, J. C. Kentish, and P. Eaton
Oxidant-induced Activation of Type I Protein Kinase A Is Mediated by RI Subunit Interprotein Disulfide Bond Formation
J. Biol. Chem., August 4, 2006; 281(31): 21827 - 21836.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
L. Willems, K. J. Ashton, and J. P. Headrick
Adenosine-mediated cardioprotection in the aging myocardium
Cardiovasc Res, May 1, 2005; 66(2): 245 - 255.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. P. Headrick, B. Hack, and K. J. Ashton
Acute adenosinergic cardioprotection in ischemic-reperfused hearts
Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818.
[Abstract] [Full Text] [PDF]

Home page
 Card Surg AdultHome page
R. M. Mentzer Jr., M. S. Jahania, and R. D. Lasley
Myocardial Protection
Card. Surg. Adult, January 1, 2003; 2(2003): 413 - 438.
[Full Text]

Home page
 Cardiovasc ResHome page
K. Mubagwa and W. Flameng
Adenosine, adenosine receptors and myocardial protection: An updated overview
Cardiovasc Res, October 1, 2001; 52(1): 25 - 39.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. Peart, G. Paul Matherne, R. J. Cerniway, and J. P. Headrick
Cardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart
Cardiovasc Res, October 1, 2001; 52(1): 120 - 129.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Guo, W. R. Giles, and C. A. Ward
Effect of hydrogen peroxide on the membrane currents of sinoatrial node cells from rabbit heart
Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H992 - H999.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
H. T. Lee and C. W. Emala
Adenosine attenuates oxidant injury in human proximal tubular cells via A1 and A2a adenosine receptors
Am J Physiol Renal Physiol, May 1, 2002; 282(5): F844 - F852.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics.