© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Effect of cardiac A1 adenosine receptor overexpression on sarcoplasmic reticulum function
aDepartimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, 56126 Pisa, Italy
bDepartment of Pediatrics and the Cardiovascular Research Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
cDepartment of Pediatrics, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
* Corresponding author r.zucchi{at}med.unipi.it
Objective: We investigated the effect of A1 adenosine receptor overexpression, which has been reported to increase myocardial tolerance to ischemia-reperfusion injury, on sarcoplasmic reticulum (SR) Ca2+ handling. Methods: Transgenic mouse hearts (
300-fold A1 adenosine receptor overexpression) and wild-type mouse hearts were perfused in the Langendorff mode and subjected either to 80 min of aerobic perfusion or to 30 min of aerobic perfusion, 20 min of global ischemia and 30 min of reperfusion. The hearts were then homogenized and used to assay SR oxalate-supported 45Ca2+ uptake and [3H]–ryanodine binding. Results: Transgenic hearts showed increased resistance to ischemia-reperfusion, as shown by lower diastolic tension (1.5±0.2 vs. 2.6±0.1 g, P<0.05) and higher recovery of developed tension (45±3 vs. 30±4% of the baseline, P<0.05) following ischemia-reperfusion. Under baseline conditions, oxalate-supported 45Ca2+ uptake was lower in transgenic hearts, owing to reduced Vmax (10.6±2.0 vs. 17.8±2.7 nmol/min per mg of protein, P<0.05), and the difference was preserved after ischemia-reperfusion (10.0±1.0 vs. 15.7±2.5 nmol/min per mg of protein, P<0.05). No significant difference in [3H]–ryanodine binding was observed. Conclusions: A1 adenosine receptor overexpression is associated with a decreased rate of active Ca2+ transport into the SR. We hypothesize that changes in SR function may cause a depletion of the SR Ca2+ pool, which might protect from ischemic injury by delaying the development of cytosolic Ca2+ overload during ischemia.
KEYWORDS Adenosine; Ca-pump; Ischemia; Receptors; Reperfusion; SR (function)
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. C. Pingle, S. Jajoo, D. Mukherjea, L. F. Sniderhan, K. A. Jhaveri, A. Marcuzzi, L. P. Rybak, S. B. Maggirwar, and V. Ramkumar Activation of the Adenosine A1 Receptor Inhibits HIV-1 Tat-Induced Apoptosis by Reducing Nuclear Factor-{kappa}B Activation and Inducible Nitric-Oxide Synthase Mol. Pharmacol., October 1, 2007; 72(4): 856 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Funakoshi, L. C. Zacharia, Z. Tang, J. Zhang, L. L. Lee, J. C. Good, D. E. Herrmann, Y. Higuchi, W. J. Koch, E. K. Jackson, et al. A1 Adenosine Receptor Upregulation Accompanies Decreasing Myocardial Adenosine Levels in Mice With Left Ventricular Dysfunction Circulation, May 1, 2007; 115(17): 2307 - 2315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Jaehnig, A. B. Heidt, S. B. Greene, I. Cornelissen, and B. L. Black Increased Susceptibility to Isoproterenol-Induced Cardiac Hypertrophy and Impaired Weight Gain in Mice Lacking the Histidine-Rich Calcium-Binding Protein Mol. Cell. Biol., December 15, 2006; 26(24): 9315 - 9326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, J. Petranka, K. Yamamura, R. E. London, C. Steenbergen, and E. Murphy Gender differences in sarcoplasmic reticulum calcium loading after isoproterenol Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2657 - H2662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Said, L. Vittone, C. Mundina-Weilenmann, P. Ferrero, E. G. Kranias, and A. Mattiazzi Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1198 - H1205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mubagwa Does adenosine protect the heart by acting on the sarcoplasmic reticulum? Cardiovasc Res, February 1, 2002; 53(2): 286 - 289. [Full Text] [PDF]
|
|