Current knowledge on the role of P2Y receptors in cardioprotection against ischemia-reperfusion

Djerada, Zoubir; Féliu, Catherine; Richard, Vincent; Millart, Hervé

doi:10.1016/j.phrs.2016.08.009

Cited by 22 publications

(57 citation statements)

References 111 publications

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“…125 It was concluded in a recent review that P2Y receptors play an important role as a therapeutic target in myocardial protection during ischemia/reperfusion. 126 The P2X4 receptor is needed for neuroprotection via ischemic preconditioning. 127 An increase in expression of P2X3 receptors in superior cervical ganglia and dorsal root ganglion neurons was also reported, leading to aggravated sympathoexcitatory reflexes.…”

Section: Heart Diseasesmentioning

confidence: 99%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

324

295

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Abstract:There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y 1 , P2Y 12 , and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine. (Circ Res. 2017;120:207-228.

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Section: Heart Diseasesmentioning

confidence: 99%

Purinergic Signaling in the Cardiovascular System

Burnstock

2017

Circulation Research

324

295

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“…ATP released from the ischaemic myocardium causes reflex responses mediated by cardiac sympathetic afferent nerves ( Dong et al, 2016 ). P2YR are important therapeutic targets in myocardial protection during ischemia/reperfusion ( Djerada et al, 2017 ). P2Y 6 R could be a therapeutic target to regulate cardiac hypertrophy ( Clouet et al, 2016 ).…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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“…Signaling via P2X receptors has been shown to be detrimental in cardiovascular IRI, and blockade of P2X7 receptors reverses vasomotor dysfunction in saphenous vein grafts during coronary artery bypass . Although mainstay antithrombotic therapies act by blocking the P2Y12‐mediated aggregation of platelets, growing evidence has revealed a potential protective role for P2Y receptor signaling in cardiac IRI . Here, direct agonism of P2Y2 receptors by exogenous uridine‐5'‐triphosphate (UTP) reduces infarct size and functional deficits in a rat model of myocardial infarction, and inhibition of P2Y receptors blocks the protective effects of UTP‐mediated purinergic signaling .…”

Section: Targeting Atp In Iri and Graft Preservationmentioning

confidence: 99%

“…38 Although mainstay antithrombotic therapies act by blocking the P2Y12-mediated aggregation of platelets, growing evidence has revealed a potential protective role for P2Y receptor signaling in cardiac IRI. 39 Here, direct agonism of P2Y2 receptors by exogenous uridine-5'-triphosphate (UTP) reduces infarct size and functional deficits in a rat model of myocardial infarction, 40 and inhibition of P2Y receptors blocks the protective effects of UTP-mediated purinergic signaling. 41 Recent work has also elucidated a role for P2X receptors in cardioprotection, and pretreatment with P2X7 receptor agonists during ischemic preconditioning has been shown to be protective in cardiac IRI, possibly via a mechanism whereby Panx1 channels and P2X7 receptor form a complex that, in response to exogenous ATP or P2X7 receptor agonists, activate downstream signals that cause the release of cardioprotective molecules including sphingosine-1-phosphate.…”

Section: A3rmentioning

confidence: 99%

Extracellular nucleotide signaling in solid organ transplantation

Yeudall

Leitinger

Laubach

2020

American Journal of Transplantation

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The role of extracellular purine nucleotides, including adenosine triphosphate (ATP) and adenosine, as modulators of posttransplantation outcome and ischemia‐reperfusion injury is becoming increasingly evident. Upon pathological release of ATP, binding and activation of P2 purinergic surface receptors promote tissue injury and inflammation, while the expression and activation of P1 receptors for adenosine have been shown to attenuate inflammation and limit ischemia‐induced damage, which are central to the viability and long‐term success of allografts. Here we review the current state of the transplant field with respect to the role of extracellular nucleotide signaling, with a focus on the sources and functions of extracellular ATP. The connection between ischemia reperfusion, purinergic signaling, and graft preservation, as well as the role of ATP and adenosine as driving factors in the promotion and suppression of posttransplant inflammation and allograft rejection, are discussed. We also examine novel therapeutic approaches that take advantage of the ischemia‐reperfusion‐responsive and immunomodulatory roles for purinergic signaling with the goal of enhancing graft viability, attenuating posttransplant inflammation, and minimizing complications including rejection, graft failure, and associated comorbidities.

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Current knowledge on the role of P2Y receptors in cardioprotection against ischemia-reperfusion

Cited by 22 publications

References 111 publications

Purinergic Signaling in the Cardiovascular System

Purinergic Signaling in the Cardiovascular System

Purinergic Signalling: Therapeutic Developments

Extracellular nucleotide signaling in solid organ transplantation

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