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

Aim: Diadenosine polyphosphates are present intracellularly and in extracellular fluid due to release from secretory vesicles in platelets, chromaffin cells and other cells. This study investigates effects of diadenosine pentaphosphate (AP(5)A) on heart muscle function. Methods: Contractile force amplitude and action potential duration at 90% repolarization (APD(90)) were measured after challenge with AP(5)A 50 mum or isoproterenol 50-70 nM in guinea pig papillary muscles. Isoproterenol was given immediately after AP(5)A-exposure or after 45 min washout. AP(5)A was combined with antagonists to the purinergic P2 receptor (suramin 100 mum), the dinucleotide receptor [diinosine pentaphosphate 30 mum (IP5I)] or adenosine receptors [8-(P-sulfophenyl) theophylline 50 mum (8-SPT)]. Results: Results are %-change (mean +/- SEM) from value before exposure. AP(5)A increased contractile force by 22 +/- 3%* (*P < 0.05), and IP5I abolished this. AP(5)A prolonged APD(90) by 7 +/- 2%*. AP(5)A significantly reduced response to isoproterenol acutely from 31 +/- 4* (controls) to 9 +/- 4% and after 45 min washout from 61 +/- 14* (controls) to 16 +/- 5%. 8-SPT abolished the sustained effect. Increase in contractile force by AP(5)A was confirmed in human atria trabecula preparations. Conclusion: AP(5)A increased contractile force and prolonged APD(90). Contractile force increased by stimulation of the dinucleotide receptor in guinea pig myocardium. The sustained anti-beta-adrenergic effect of AP(5)A was due to adenosine receptor stimulation.