ArticleCirculation research2006
Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y2 and P2Y6 receptors on cardiomyocytes and release of UTP in man during myocardial infarction.
Article in Circulation research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 96 citations in OpenAlex.
- Development of cardiovascular and all-cause mortality risk prediction models for maintenance hemodialysis patients based on metabolomics.BMC nephrology · 2025Article
- Cardiac function of colorectal cancer mice is remotely controlled by gut microbiota: regulating serum metabolites and myocardial cytokines.Animal microbiome · 2025Article
- Functionalized Congeners of 2Cells · 2024Article
- Synthesis and pharmacological characterization of multiply substituted 2H-chromene derivatives as P2YBioorganic & medicinal chemistry letters · 2022Article
- Adipocyte purinergic receptors activated by uracil nucleotides as obesity and type 2 diabetes targets.Current opinion in pharmacology · 2022Review
- Structure-activity relationships of pyrimidine nucleotides containing a 5'-α,β-methylene diphosphonate at the P2YBioorganic & medicinal chemistry letters · 2021Article
- Positive Inotropic Effects of ATP ReleasedFrontiers in cell and developmental biology · 2021Article
- Impaired UTP-induced relaxation in the carotid arteries of spontaneously hypertensive rats.Purinergic signalling · 2020Article
- The role of purinergic P2YPurinergic signalling · 2020Article
- Stimulation of P2Y11 receptor protects human cardiomyocytes against Hypoxia/Reoxygenation injury and involves PKCε signaling pathway.Scientific reports · 2019Article
- On inotropic effects of UTP in the human heart.Heliyon · 2019Review
- Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production.International journal of molecular sciences · 2019Review
- Association of G-protein coupled purinergic receptor P2Y2 with ischemic stroke in a Han Chinese population of North China.Neural regeneration research · 2019Article
- Pyrimidine Nucleotides Containing a (S)-Methanocarba Ring as P2YMedChemComm · 2017Article
- Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy.The Journal of biological chemistry · 2016Article
- Cardiac purinergic signalling in health and disease.Purinergic signalling · 2015Review
- The effect of purinergic P2 receptor blockade on skeletal muscle exercise hyperemia in miniature swine.European journal of applied physiology · 2014Article
- Cellular mechanisms of tissue fibrosis. 6. Purinergic signaling and response in fibroblasts and tissue fibrosis.American journal of physiology. Cell physiology · 2014Review
- Adenosine diphosphate reduces infarct size and improves porcine heart function after myocardial infarct.Physiological reports · 2013Article
- Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity.Journal of molecular and cellular cardiology · 2012Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The aim of this study was to examine a possible role for extracellular pyrimidines as inotropic factors for the heart. First, nucleotide plasma levels were measured to evaluate whether UTP is released in patients with coronary heart disease. Then, inotropic effects of pyrimidines were examined in isolated mouse cardiomyocytes. Finally, expression of pyrimidine-selective receptors (a subgroup of the P2 receptors) was studied in human and mouse heart, using real time polymerase chain reaction, Western blot, and immunohistochemistry. Venous plasma levels of UTP were increased (57%) in patients with myocardial infarction. In electrically stimulated cardiomyocytes the stable P2Y(2/4) agonist UTPgammaS increased contraction by 52%, similar to beta1-adrenergic stimulation with isoproterenol (65%). The P2Y6-agonist UDPbetaS also increased cardiomyocyte contraction (35%), an effect abolished by the P2Y6-blocker MRS2578. The phospholipase C inhibitor U73122 inhibited both the UDPbetaS and the UTPgammaS-induced inotropic effect, indicating an IP3-mediated effect via P2Y6 receptors. The P2Y14 agonist UDP-glucose was without effect. Quantification of mRNA with real time polymerase chain reaction revealed P2Y2 as the most abundant pyrimidine receptor expressed in cardiomyocytes from man. Presence of P2Y6 receptor mRNA was detected in both species and confirmed at protein level with Western blot and immunohistochemistry in man. In conclusion, UTP levels are increased in humans during myocardial infarction, giving the first evidence for UTP release in man. UTP is a cardiac inotropic factor most likely by activation of P2Y2 receptors in man. For the first time we demonstrate inotropic effects of UDP, mediated by P2Y6 receptors via an IP3-dependent pathway. Thus, the extracellular pyrimidines (UTP and UDP) could be important inotropic factors involved in the development of cardiac disease.
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