title: A positive inotropic effect of UTP in the human cardiac atrium.
abstract: In the cardio-vascular system extracellular UTP can induce receptor-mediated vasoconstriction via smooth muscle cells and vasodilatation via endothelial cells. We evaluated inotropic effects of UTP in preparations from human heart. Contractile effects were studied in atrial preparations from patients undergoing cardiac bypass surgery. For comparison, contractility in isolated spontaneously beating right atrial and paced left atrial preparations from mice was investigated. UTP and UTPγS concentration-dependently exerted a positive inotropic effect with a maximum at 100 µM UTP that amounted to 156% of pre-drug value (n=13) without changing time parameters of contraction. UTP was able to partially attenuate the positive inotropic effect of β-adrenoceptor stimulation. UTP did not change the beating rate in right atrial mouse preparations. The positive inotropic effect of UTP could not be blocked by the P2 purinoceptor antagonists suramin (100 µM and 500 µM), PPADS (50 µM) and reactive blue (100 µM). Likewise inhibitors of PLC activity (U73122) and of adenylyl cyclase activity (SQ22563; 10 µM each) failed to affect the effects of UTP. In summary, we describe a novel positive inotropic effect of UTP on force contraction in the isolated human atrium. We tentatively suggest that UTP might act via P2Y2- or P2Y4-like receptors.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097 Halle, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gergs
authors.affiliation: Klinik für Herz-und Thoraxchirurgie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097 Halle, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.affiliation: Klinik für Herz-und Thoraxchirurgie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097 Halle, Germany.
authors.forename: Hasan
authors.initials: H
authors.lastname: Bushnaq
authors.affiliation: Klinik für Herz-und Thoraxchirurgie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097 Halle, Germany.
authors.forename: Rolf-Edgar
authors.initials: RE
authors.lastname: Silber
authors.affiliation: Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097 Halle, Germany. Electronic address: joachim.neumann@medizin.uni-halle.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Neumann
mesh_terms: D000368:Aged; D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004452:Echocardiography; D004562:Electrocardiography; D006325:Heart Atria / Q000000981:diagnostic imaging / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008875:Middle Aged; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D014544:Uridine Triphosphate
keywords: Contractility; Human heart; P2Y receptor; Right atrium