title: Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors.
abstract: Diadenosine polyphosphates (Ap(n)As) are endogenously produced molecules which have been identified in various tissues of mammalian organism, including myocardium. Ap(n)As contribute to the blood clotting and are also widely accepted as regulators of blood vascular tone. Physiological role of Ap(n)As in cardiac muscle has not been completely elucidated. The present study aimed to investigate the effects of diadenosine tetra- (Ap4A) and penta- (Ap5A) polyphosphates on contractile function and action potential (AP) waveform in rat supraventricular and ventricular myocardium. We have also demonstrated the effects of A4pA and Ap5A in myocardial sleeves of pulmonary veins (PVs), which play a crucial role in genesis of atrial fibrillation. APs were recorded with glass microelectrodes in multicellular myocardial preparations. Contractile activity was measured in isolated Langendorff-perfused rat hearts. Both Ap4A and Ap5A significantly reduced contractility of isolated Langendorff-perfused heart and produced significant reduction of AP duration in left and right auricle, interatrial septum, and especially in right ventricular wall myocardium. Ap(n)As also shortened APs in rat pulmonary veins and therefore may be considered as potential proarrhythmic factors. Cardiotropic effects of Ap4A and Ap5A were strongly antagonized by selective blockers of P2 purine receptors suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), while P1 blocker DPCPX was not effective. We conclude that Ap(n)As may be considered as new class of endogenous cardioinhibitory compounds. P2 purine receptors play the central role in mediation of Ap4A and Ap5A inhibitory effects on electrical and contractile activity in different regions of the rat heart.
authors.affiliation: Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye gory 1, building 12, Moscow, 119991, Russia.|Department of Physiology, Pirogov Russian National Research Medical University, Ostrovitjanova 1, Moscow, 117997, Russia.
authors.forename: Ksenia B
authors.initials: KB
authors.lastname: Pustovit
authors.affiliation: Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye gory 1, building 12, Moscow, 119991, Russia.|Department of Physiology, Pirogov Russian National Research Medical University, Ostrovitjanova 1, Moscow, 117997, Russia.
authors.forename: Vladislav S
authors.initials: VS
authors.lastname: Kuzmin
authors.affiliation: Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye gory 1, building 12, Moscow, 119991, Russia. abram340@mail.ru.|Department of Physiology, Pirogov Russian National Research Medical University, Ostrovitjanova 1, Moscow, 117997, Russia. abram340@mail.ru.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Abramochkin
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology
chemical_list: D015226:Dinucleoside Phosphates; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; D011732:Pyridoxal Phosphate; D013498:Suramin
keywords: Action potential; Contraction; Heart; Polyphosphates; Purine receptors; Rat