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- Erlinge, David, et al.
(författare)
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Uridine triphosphate (UTP) is released during cardiac ischemia
- 2005
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Ingår i: Int J Cardiol. - : Elsevier BV. - 0167-5273. ; 100:3, s. 427-33
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Extracellular uridine triphosphate (UTP) stimulates vasodilatation, automaticity in ventricular myocytes and release of tissue-plasminogen activator (t-PA), indicating that UTP may be important in cardiac regulation. We took advantage of a recently developed quantitative assay for UTP to test the hypothesis that UTP is released in the circulation during cardiac ischemia. METHODS: In ten pigs, a balloon catheter in the left anterior descending artery was introduced to induce ischemia. Samples were collected from the coronary sinus. Blood flow in the coronary sinus was assessed by a Doppler velocity transducer. RESULTS: Plasma UTP levels increased early during ischemia and early after reperfusion (by 257+/-100 and 247+/-72%, p<0.05). Cardiac blood flow, ventricular arrhythmias and t-PA release were markedly increased at the same time points. In contrast, after 30 min, a second period of ischemia did not result in any significant increase of UTP or blood flow. Furthermore, ventricular arrhythmias were less frequent. UTP levels correlated with ventricular arrhythmia and blood flow. Similar results were found for ATP. CONCLUSION: For the first time we have shown that UTP is released during cardiac ischemia. UTP released during ischemia may stimulate blood flow, arrhythmia and t-PA release.
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| 2. |
- Wihlborg, Anna-Karin, et al.
(författare)
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Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y(2) and P2Y(6) receptors on cardiomyocytes and release of UTP in man during myocardial infarction
- 2006
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Ingår i: Circulation Research. - 0009-7330. ; 98:7, s. 970-976
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Tidskriftsartikel (refereegranskat)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 UTP gamma S increased contraction by 52%, similar to beta(1)-adrenergic stimulation with isoproterenol (65%). The P2Y(6)-agonist UDP gamma S also increased cardiomyocyte contraction (35%), an effect abolished by the P2Y(6)-blocker MRS2578. The phospholipase C inhibitor U73122 inhibited both the UDP beta S and the UTP gamma S-induced inotropic effect, indicating an IP3-mediated effect via P2Y(6) receptors. The P2Y(14) agonist UDP-glucose was without effect. Quantification of mRNA with real time polymerase chain reaction revealed P2Y(2) as the most abundant pyrimidine receptor expressed in cardiomyocytes from man. Presence of P2Y(6) 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 P2Y(2) receptors in man. For the first time we demonstrate inotropic effects of UDP, mediated by P2Y(6) 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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