Increase in cardiac P2X1- and P2Y2-receptor mRNA levels in congestive heart failure

Hou, Mingyan; Malmsjö, Malin; Möller, Sebastian; Pantev, Emil; Bergdahl, Anders; Zhao, Xiao-He; Sun, Xingshu; Hedner, Thomas; Edvinsson, Lars; Erlinge, David

doi:10.1016/s0024-3205(99)00353-7

Cited by 58 publications

(47 citation statements)

References 26 publications

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“…In vitro studies of mouse cardiomyocytes demonstrated a positive inotropic effect of ATP stimulation via the P2Y 11 receptor [45]. In the cardiomyocyte of rats, mRNA for the P2Y 11 receptor was detected in both atria and ventricle [46]. Thus, P2Y 11 might also be involved in contractility receptors in human skeletal muscle cells.…”

Section: Discussionmentioning

confidence: 96%

Purinergic receptors expressed in human skeletal muscle fibres

Bornø

Ploug

Bune

et al. 2011

Purinergic Signalling

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Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and agematched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy in immunolabelled transverse sections of muscle biopsies. The receptors P2Y 4 , P2Y 11 and likely P2X 1 were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X 1 receptors were expressed in intracellular vesicles and sarcolemma. P2Y 4 receptors were present in sarcolemma. P2Y 11 receptors were abundantly and diffusely expressed intracellularly and were more explicitly expressed in type I than in type II fibres, whereas P2X 1 and P2Y 4 showed no fibre-type specificity. Both diabetic patients and healthy controls showed similar distribution of receptors. The current study demonstrates that purinergic receptors are located intracellularly in human skeletal muscle fibres. The similar cellular localization of receptors in healthy and diabetic subjects suggests that diabetes is not associated with an altered distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.

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Section: Discussionmentioning

confidence: 96%

Purinergic receptors expressed in human skeletal muscle fibres

Bornø

Ploug

Bune

et al. 2011

Purinergic Signalling

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“…6) [488]. Enhanced P2YR-mediated dilatation by endothelium-derived hyperpolarising factor was also described in congestive heart failure [489].…”

Section: Pathophysiology and Therapeutic Potentialmentioning

confidence: 96%

“…The left set represents a sham operated rat and the right the CHF rat. There is a clear shift in the equivalence point (arrow) in the CHF rat towards the right (higher concentration) for both the P2X1 and P2Y 2 receptor (reproduced from [488], with permission from Elsevier)…”

Section: Ischaemiamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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“…Upregulation of P2X 1 and P2Y 2 receptor mRNA in the hearts of rats with congestive heart failure has been reported 40 . Further therapeutic targets for P2 receptor agonists and antagonists include congestive heart failure, hypertension, stroke and angina.…”

Section: Cardiovascular Systemmentioning

confidence: 98%

Potential therapeutic targets in the rapidly expanding field of purinergic signalling

Burnstock

2002

Clinical Medicine

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-The concept of a purinergic signalling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief historical review and update of purinoceptor subtypes, this article focuses on the diverse physiological roles of adenosine triphosphate, adenosine diphosphate, uridine triphosphate and adenosine. These molecules mediate short-term (acute) signalling functions in neurotransmission, secretion and vasodilation, and long-term (chronic) signalling functions in development, regeneration, proliferation and cell death. Plasticity of purinoceptor expression in pathological conditions is frequently obser ved, including an increase in the purinergic component of parasympathetic nervous control of the human bladder in interstitial cystitis and outflow obstruction, and in sympathetic cotransmitter control of blood vessels in hypertensive rats. The antithrombotic action of clopidogrel (Plavix), a P2Y 12 receptor antagonist, has been shown to be particularly promising in the prevention of recurrent strokes and heart attacks in recent clinical trials (CAPRIE and CURE). The role of P2X 3 receptors in nociception and a new hypothesis concerning purinergic mechanosensory transduction in visceral pain will be considered, as will the therapeutic potential of purinergic agonists or antagonists for the treatment of supraventricular tachycardia, cancer, dry eye, bladder hyperactivity, erectile dysfunction, osteoporosis, diabetes, gut motility and vascular disorders. KEY WORDS: purinoceptors, interstitial cystitis, thrombosis, visceral pain, cancer, osteoporosis, peripheral vascular disease, cystic fibrosis, Parkinson' s disease, kidney failure Purinergic signalling: history and receptor subtypes A seminal paper by Drury and Szent-Györgi in 1929 described the potent actions of purine nucleotides and nucleosides, adenosine triphosphate (ATP) and adenosine on the heart and blood vessels 1 . A landmark paper by Pamela Holton in 1959 showed that, during antidromic stimulation of sensory nerves, ATP was released to the rabbit ear artery in sufficient amounts to produce changes in vascular tone 2 . Then, in 1970, Burnstock et al. found evidence for the role of ATP as a neurotransmitter in nonadrenergic, noncholinergic (NANC) nerves supplying the gut 3 , and, in 1972, the word 'purinergic' was coined and the purinergic-neurotransmission hypothesis was put forward 4 (Fig 1). This concept met with considerable resistance for many years because ATP had been established as an intracellular energy source involved in various metabolic cycles, and it was thought that such a ubiquitous molecule was unlikely to be involved in selective extracellular signalling. However, the concept is now widely accepted. Later, it was established that ATP is a cotransmitter with classical transmitters in both the peripheral and the central nervous systems, and that purines are powerful extracellular messengers to non-neuronal cells, including exocrine and endocrine, secretory, endothelial, b...

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Increase in cardiac P2X1- and P2Y2-receptor mRNA levels in congestive heart failure

Cited by 58 publications

References 26 publications

Purinergic receptors expressed in human skeletal muscle fibres

Purinergic receptors expressed in human skeletal muscle fibres

Cardiac purinergic signalling in health and disease

Potential therapeutic targets in the rapidly expanding field of purinergic signalling

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