A3 adenosine receptor stimulation modulates sarcoplasmic reticulum Ca2+ release in rat heart

Zucchi, Riccardo; Yu, Gongyuan; Ghelardoni, Sandra; Ronca, Francesca; Ronca-Testoni, S

doi:10.1016/s0008-6363(00)00318-7

Cited by 38 publications

(20 citation statements)

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“…Reduced SERCA expression at the age of 14 weeks in mice is consistent with a previous report of decreased SERCA mRNA levels in the ventricles of mice [6]. This may contribute to reduced force of contraction in isolated atria of A 3 high mice, in addition to a potential regulation of calcium release by A 3 adenosine receptors [29]. Our findings indicate that atrial and left ventricular dilatation and dysfunction in mice develop over time and may be the morphological and functional reflections of a brady-cardiomyopathy.…”

Section: Atrial Arrhythmias Pave the Way For Atrial And Ventricular Csupporting

confidence: 91%

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors

Fabritz

Kirchhof

Fortmüller

et al. 2004

Cardiovascular Research

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Objective-An increased expression of adenosine receptors is a promising target for gene therapy aimed at protecting the myocardium against ischemic damage, but may alter cardiac electrophysiology. We therefore studied the effects of heart-directed overexpression of A 3 adenosine receptors (A 3 ARs) at different gene doses on sinus and atrio-ventricular (AV) nodal function in mice.Methods and results-Mice with heart-specific overexpression of A 3 AR at high ( ) or low ( ) levels and their wild-type littermates were studied. Telemetric electrocardiogram (ECG) recordings in adult freely moving mice showed profound sinus bradycardia resulting in either ventricular escape rhythms or an incessant bradycardia-tachycardia syndrome (minimal heart rate 217 ±25*; WT 406 ±21 beats/min, all values as mean ±S.E.M., n = 7 per genotype, *p < 0.05). Exercise attenuated bradycardia in mice (maximal heart rate 650 ±13*; WT 796 ±13 beats/min) and first-degree AV nodal block was present (PQ interval 36 ±4*; WT 23 ±5 ms). Isolated hearts showed complete heart block (10/17 * vs. 1/17 WT). Atrial bradycardia and AV block were already present 3 weeks after birth. Doppler echocardiography revealed atrial dysfunction and progressive atrial enlargement that was moderate at 3 and 8 weeks, and progressed at 12 and 21 weeks of age (all p < 0.05 vs. WT). Atrial contractility and sarcoendoplasmic Ca 2 + ATPase (SERCA) 2a protein expression were reduced in isolated left atria at the age of 14 weeks. Fibrosis was present in left atria at 14 weeks, but not at 5 weeks of age. mice had first-degree AV block without arrhythmias or structural changes. Conclusions-Heart-directed

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Section: Atrial Arrhythmias Pave the Way For Atrial And Ventricular Csupporting

confidence: 91%

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors

Fabritz

Kirchhof

Fortmüller

et al. 2004

Cardiovascular Research

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“…Effects of A 2 antagonists are restricted to in situ models consistent with A 2 receptors modulating inflammatory processes and platelet aggregation, requiring the presence of blood-borne elements. As already noted A 2A AR activation fails to protect isolated cardiomyocytes (24) or blood-free perfused hearts (75,224,317).…”

Section: Endogenous Versus Exogenous (Pharmacological) Cardioprotectionmentioning

confidence: 59%

“…Two other investigations in isolated perfused hearts do provide support for direct A 2A AR-mediated protection in the rat (182) and rabbit (35) myocardium. These latter studies contrast others that find no protection with A 2 agonism in isolated hearts (75,224,317). Moreover, A 2A AR activation fails to protect isolated cardiomyocytes (24).…”

Section: Adenosine Receptor-mediated Cardioprotection: Which Subtypesmentioning

confidence: 75%

“…Postischemic protection observed with A 2 agonism appears to involve attenuation of neutrophil activity, oxidant stress, and inflammation. However, again there is also evidence that postischemic adenosine protects in blood-free models (75,86,225,317). Additionally, whereas recent studies indicate A 3 AR activation on reperfusion limits neutrophil-mediated reperfusion injury in vivo (133) and apoptotic death and injury in isolated hearts and cardiomyocytes (188), there is also evidence for minimal postischemic protection in isolated hearts (77).…”

Section: Protection Against Reversible Versus Irreversible Injuries Mmentioning

confidence: 99%

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Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Headrick

Hack

Ashton

2003

American Journal of Physiology-Heart and Circulatory Physiology

150

164

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. Acute adenosinergic cardioprotection in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 285: H1797-H1818, 2003; 10.1152/ajpheart.00407. 2003.-Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5Ј-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.adenosine; adenosine receptor activation; ischemia; reperfusion injury THE HEART possesses its own intrinsic protective responses, including the adenosine receptor system, which enhance resistance to ischemic insult. An understanding of the mechanisms involved in these responses not only informs us of how the heart reacts to injurious stimuli, but may provide avenues for developing novel protective strategies applicable in the setting of ischemia-reperfusion. The purine nucleoside adenosine was attributed with cardioregulatory functions almost 75 years ago (64), and since then has emerged as a crucially important control substance in essentially every tissue of the body. In the heart adenosine not only plays a role in regulating growth and differentiation, angiogenesis, coronary blood flow, cardiac conduction and heart rate, substrate metabolism, and sensitivity to adrenergic stimulation (23,67,68,73,74,260,271,283), but may play a role as an endogenous determinant of ischemic tolerance (189,225,245,259,311,312,318). From a therapeutic viewpoint, adenosine-based therapies protect against ischemic injury in a variety of animal models (72,177,208,265,288) and in human cardiac tissue (34, 36, 37,240,296). However, much remains unclear regarding the roles and mechanisms of action of adenosine in producing acute protection against ischemia and reperfusion. Generation of Endogenous Adenosine During InsultEndogenous adenosine levels increase rapidly with ischemic insult (104,109,285,286) to mediate a retaliatory response. This protective pool of adenosine can be formed via dephosphorylation of 5Ј-AMP by intra-and extracellular 5Ј-nucleotidases and from S-adenosylhomocysteine (SAH) via SAH hydrolase. Extracellular adenosine is rapidly taken into cells via a facilitative transporter (131). Within cells it is either deaminated by adenosine deaminase or rephosphorylated to 5Ј-AMP via adenosine kinase. O...

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“…Adenosine receptors (ARs) exist in at least four different subtypes including A 1 , A 2A , A 2B , and A 3 (28,34). The recently identified A 3 AR (A 3 R), like the A 1 R, negatively couples to adenylyl cyclase and displays significant cardioprotective activity (2,36,38,(45)(46)(47)49).…”

mentioning

confidence: 99%

Role of adenosine A₁ and A₃ receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury

Shneyvays¹,

Leshem²,

Zinman³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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A3 adenosine receptor stimulation modulates sarcoplasmic reticulum Ca2+ release in rat heart

Abstract: A3 adenosine receptor stimulation modulates the SR Ca(2+) channel. This action might account for the protective effect of adenosine.

Cited by 38 publications

References 37 publications

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Role of adenosine A₁ and A₃ receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury

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A3 adenosine receptor stimulation modulates sarcoplasmic reticulum Ca2+ release in rat heart

Abstract: A3 adenosine receptor stimulation modulates the SR Ca(2+) channel. This action might account for the protective effect of adenosine.

Cited by 38 publications

References 37 publications

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Role of adenosine A1 and A3 receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury

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Role of adenosine A₁ and A₃ receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury