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P2Y4 and cardiomyocytes

Ulrich Gergs, Daniel Rothkirch, Britt Hofmann, Hendrik Treede, Bernard Robaye, Andreas Simm, Christa E Müller, Joachim Neumann
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather than transient. In the present study, we tried to elucidate the underlying receptor and signal transduction for this effect of UTP. Therefore, we measured the effect of UTP on force of contraction, phosphorylation of p38 and ERK1/2, in human atrial preparations, atrial preparations from genetically modified mice, cardiomyocytes from adult mice and cardiomyocytes from neonatal rats...
July 5, 2018: European Journal of Pharmacology
Sophie Clouet, Larissa Di Pietrantonio, Evangelos-Panagiotis Daskalopoulos, Hrag Esfahani, Michael Horckmans, Marion Vanorlé, Anne Lemaire, Jean-Luc Balligand, Christophe Beauloye, Jean-Marie Boeynaems, Didier Communi
The study of the mechanisms leading to cardiac hypertrophy is essential to better understand cardiac development and regeneration. Pathological conditions such as ischemia or pressure overload can induce a release of extracellular nucleotides within the heart. We recently investigated the potential role of nucleotide P2Y receptors in cardiac development. We showed that adult P2Y4-null mice displayed microcardia resulting from defective cardiac angiogenesis. Here we show that loss of another P2Y subtype called P2Y6, a UDP receptor, was associated with a macrocardia phenotype and amplified pathological cardiac hypertrophy...
July 22, 2016: Journal of Biological Chemistry
Safoura Mazrouei, Fatemeh Sharifpanah, Mohamed M Bekhite, Hans-Reiner Figulla, Heinrich Sauer, Maria Wartenberg
Purinergic signaling may be involved in embryonic development of the heart. In the present study, the effects of purinergic receptor stimulation on cardiomyogenesis of mouse embryonic stem (ES) cells were investigated. ADP or ATP increased the number of cardiac clusters and cardiac cells, as well as beating frequency. Cardiac-specific genes showed enhanced expression of α-MHC, MLC2v, α-actinin, connexin 45 (Cx45), and HCN4, on both gene and protein levels upon ADP/ATP treatment, indicating increased cardiomyogenesis and pacemaker cell differentiation...
December 2015: Purinergic Signalling
Kwok-Kuen Cheung, Camila Marques-da-Silva, Leandro Vairo, Danúbia Silva dos Santos, Regina Goldenberg, Robson Coutinho-Silva, Geoffrey Burnstock
Purinergic receptors activated by extracellular nucleotides (adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP)) are well known to exert physiological effects on the cardiovascular system, whether nucleotides participate functionally in embryonic heart development is not clear. The responsiveness of embryonic cardiomyocytes (E) 12 to P2 receptor agonists by measuring Ca(2+) influx did not present response to ATP, but responses to P2 agonists were detected in cardiomyocytes taken from E14 and E18 rats...
March 2015: Purinergic Signalling
Edith Hochhauser, Ronit Cohen, Maayan Waldman, Anna Maksin, Ahuva Isak, Dan Aravot, P Suresh Jayasekara, Christa E Müller, Kenneth A Jacobson, Asher Shainberg
Extracellular nucleotides acting via P2 receptors play important roles in cardiovascular physiology/pathophysiology. Pyrimidine nucleotides activate four G protein-coupled P2Y receptors (P2YRs): P2Y2 and P2Y4 (UTP-activated), P2Y6, and P2Y14. Previously, we showed that uridine 5'-triphosphate (UTP) activating P2Y2R reduced infarct size and improved mouse heart function after myocardial infarct (MI). Here, we examined the cardioprotective role of P2Y2R in vitro and in vivo following MI using uridine-5'-tetraphosphate δ-phenyl ester tetrasodium salt (MRS2768), a selective and more stable P2Y2R agonist...
December 2013: Purinergic Signalling
Michael Horckmans, Elvira Léon-Gómez, Bernard Robaye, Jean-Luc Balligand, Jean-Marie Boeynaems, Chantal Dessy, Didier Communi
Nucleotides released within the heart under pathological conditions can be involved in cardioprotection or cardiac fibrosis through the activation purinergic P2Y(2) and P2Y(6) receptors, respectively. We previously demonstrated that adult P2Y(4)-null mice display a microcardia phenotype related to a cardiac angiogenic defect. To evaluate the functional consequences of this defect, we performed here a combination of cardiac monitoring and exercise tests. We investigated the exercise capacity of P2Y(4) wild-type and P2Y(4)-null mice in forced swimming and running tests...
October 1, 2012: American Journal of Physiology. Heart and Circulatory Physiology
Smadar Yitzhaki, Vladimir Shneyvays, Kenneth A Jacobson, Asher Shainberg
Cardiomyocytes express one or more subtypes of P2 receptors for extracellular nucleotides. P2 purinoceptors, which are activated by nucleotides, are classified as P2X or P2Y: P2X receptors are ligand-gated intrinsic ion channels, and P2Y receptors are G protein-coupled receptors. Extracellular pyrimidine and purine nucleotides are released from the heart during hypoxia. Although the cardioprotective effects of purines acting via purinoceptors were studied intensively, the physiological role of uracil nucleotide-responsive P2Y2, P2Y4, P2Y6, and P2Y14 receptors is still unclear, especially in the cardiovascular system...
April 15, 2005: Biochemical Pharmacology
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