Positive inotropic and sustained anti‐<i>β</i>‐adrenergic effect of diadenosine pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and adenosine receptors

Arvola, L.; Bertelsen, Geir; Hassaf, D.; Ytrehus, Kirsti

doi:10.1111/j.1365-201x.2004.01363.x

Acta Physiologica Scandinavica

2004

DOI: 10.1111/j.1365-201x.2004.01363.x

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Positive inotropic and sustained anti‐β‐adrenergic effect of diadenosine pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and adenosine receptors

L. Arvola¹,

Geir Bertelsen²,

D. Hassaf³

et al.

Abstract: AP5A increased contractile force and prolonged APD90. Contractile force increased by stimulation of the dinucleotide receptor in guinea pig myocardium. The sustained anti-beta-adrenergic effect of AP5A was due to adenosine receptor stimulation.

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Cited by 4 publications

References 32 publications

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Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

Pustovit

Kuzmin

Abramochkin

2015

Naunyn-Schmiedeberg's Arch Pharmacol

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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.

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Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

Pustovit

Kuzmin

Abramochkin

2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier

et al. 2016

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Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10 M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node. P1 receptors antagonist DPCPX (10 M) or selective GIRK channels blocker tertiapin (10 M) completely abolished all Ap5A effects, while P2 blocker PPADS (10 M) was ineffective. Patch-clamp experiments revealed potassium inward rectifier current activated by Ap5A in guinea pig atrial myocytes. The current was abolished by DPCPX or tertiapin and therefore was considered as potassium acetylcholine-dependent inward rectifier (I ). Thus, unlike rat, in guinea pig atrium Ap5A produces activation of P1 receptors and subsequent opening of KACh channels leading to negative effects on cardiac electrical activity.

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Positive inotropic and sustained anti‐β‐adrenergic effect of diadenosine pentaphosphate in human and guinea pig hearts. Role of dinucleotide receptors and adenosine receptors

Abstract: AP5A increased contractile force and prolonged APD90. Contractile force increased by stimulation of the dinucleotide receptor in guinea pig myocardium. The sustained anti-beta-adrenergic effect of AP5A was due to adenosine receptor stimulation.

Cited by 4 publications

References 32 publications

Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

Diadenosine tetra- and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors

Cardiac purinergic signalling in health and disease

Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier

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