Abstract
Diadenosine tetraphosphate (AP4A) belongs to a wide group of naturally derived endogenous purine compounds that have recently been considered as new neurotransmitters in the autonomic nervous system. It has been shown that AP4A induces inhibitory effects and modulates adrenergic control in the heart of adult mammals. Nevertheless, the physiological significance of AP4A in early postnatal development, when sympathetic innervation remains yet immature, has not been investigated. The aim of the present study was to elucidate the effects of AP4A on the heart bioelectrical activity in early postnatal ontogenesis. Action potentials (AP) were recorded using the standard microelectrode technique in multicellular isolated right atrial (RA), left atrial (LA), and ventricle (RV) preparations from male Wistar rats at postnatal days 1, 14, and 21 and from 60-day animals that were considered as adults. The application of AP4A caused significant reduction of AP duration in atrial (RA and LA) preparations from rats of all ages. Also, AP4A caused significant AP shortening in RV preparations from rats of various ages; however, the effect was more pronounced in 21-day-old and adult rats. AP4A failed to alter automaticity of RA preparations from the rats at postnatal days 1, 14, and 21 and weakly decreased spontaneous rhythm in RA preparations from the adult rats. The effect of AP4A was partially abolished by P2-receptor blocker PPADS in LA preparations from both 21-dayold and adult rats, while it failed to suppress AP4A-caused AP shortening in preparations from 1- and 14-dayold animals. Thus, extracellular AP4A causes shortening of AP both in the atrial and ventricular myocardium in the rats of early postnatal ontogenesis and in adults. The effect of AP4A depends on age only for ventricular myocardium where it may be attributed with growing contribution of diadenosine polyphosphates to the control of myocardium inotropy.
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Szalata, M., Dinucleoside polyphosphates: Occurrence, metabolism and function, Postepy Biochem., 2001, vol. 47, no. 1, pp. 105–113.
Abramochkin, D.V., Pustovit, K.B., and Filatova, T.S., Effects of diadenosine polyphosphates on inward rectifier potassium currents in rat cardiomyocytes, Moscow Univ. Biol. Sci. Bull., 2015, vol. 70, no. 4, pp. 153–157.
Pakhomov, N.V., Pustovit, K.B., Abramochkin, D.V., and Kuz’min, V.S., The role of diadenosine pentaphosphate and nicotinamide adenine dinucleotide (NAD+) as potential nucleotide comediators in the adrenergic regulation of cardiac function, Neurochem. J., 2017, vol. 11, no. 1, pp. 63–71.
Flores, N.A., Stavrou, B.M., and Sheridan, D.J., The effects of diadenosine polyphosphates on the cardiovascular system, Cardiovasc. Res., 1999, vol. 42, no. 1, pp. 15–26.
Abramochkin, D.V., Karimova, V.M., Filatova, T.S., and Kamkin, A., Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier, J. Physiol. Sci., 2017, vol. 67, no. 4, pp. 523–529.
Hoyle, C.H., Ziganshin, A.U., Pintor, J., and Burnstock, G., The activation of P1-and P2-purinoceptors in the guinea-pig left atrium by diadenosine polyphosphates, Br. J. Pharmacol., 1996, vol. 118, no. 5, pp. 1294–1300.
Erlinge, D. and Burnstock, G., P2 receptors in cardiovascular regulation and disease, Purinergic Signal, 2008, vol. 4, no. 1, pp. 1–20.
Vassort, G., Adenosine 5'-triphosphate: A P2-purinergic agonist in the myocardium, Physiol. Rev., 2001, vol. 81, no. 2, pp. 767–806.
Pustovit, K.B., Kuzmin, V.S., and Abramochkin, D.V., Diadenosine tetra-and pentaphosphates affect contractility and bioelectrical activity in the rat heart via P2 purinergic receptors, Naunyn Schmiedebergs Arch. Pharmacol., 2016, vol. 389, no. 3, pp. 303–313.
Cheung, K.K., Ryten, M., and Burnstock, G., Abundant and dynamic expression of G protein-coupled P2Y receptors in mammalian development, Dev. Dyn., 2003, vol. 228, no. 2, pp. 254–266.
Burnstock, G. and Dale, N., Purinergic signalling during development and ageing, Purinergic Signal, 2015, vol. 11, no. 3, pp. 277–305.
Webb, T.E., Boluyt, M.O., and Barnard, E.A., Molecular biology of P2Y purinoceptors: Expression in rat heart, J. Auton. Pharmacol., 1996, vol. 16, no. 6, pp. 303–308.
Pelleg, A., Katchanov, G., and Xu, J., Autonomic neural control of cardiac function: Modulation by adenosine and adenosine-5-triphosphate, Am. J. Cardiol., 1997, vol. 79, no. 12, suppl. 1, pp. 11–14.
Neumann, J., Meissner, A., Boknik, P., Gombosová, I., Knapp, J., Lüss, H., Müller, F.U., Schlüter, H., Zidek, W., Rolf, N., Van Aken, H., Vahlensieck, U., and Schmitz, W., Inotropic effects of diadenosine tetraphosphate in isolated canine cardiac preparations, J. Cardiovasc. Pharmacol., 1999, vol. 33, no. 1, pp. 151–156.
Sawmiller, D.R., Fenton, R.A., and Dobson, J.G., Jr., Myocardial adenosine A1-receptor sensitivity during juvenile and adult stages of maturation, Am. J. Physiol., 1998, vol. 274, no. 2, pp. H627–H635.
Cothran, D.L., Lloyd, T.R., Taylor, H., Linden, J., and Matherne, G.P., Ontogeny of rat myocardial A1 adenosine receptors, Biol. Neonate, 1995, vol. 68, no. 2, pp. 111–118.
Anikina, T.A., Bilalova, G.A., Zverev, A.A., and Sitdikov, F.G., Role of P2X and P2Y receptors in rat myocardial contractility during ontogeny, Bull. Exp. Biol. Med., 2007, vol. 143, no. 6, pp. 695–698.
Anikina, T.A., Zverev, A.A., Sitdikov, F.G., and Anisimova, I.N., Interaction of adrenergic and purinergic receptors in the regulation of rat myocardial contractility in postnatal ontogeny, Russ. J. Dev. Biol., 2013, vol. 44, no. 6, pp. 296–301.
Anikina, T.A., Sitdikov, F.G., Khamzina, E.Yu., and Bilalova, G.A., Role of purinoceptors in cardiac function in rats during ontogeny, Bull. Exp. Biol. Med., 2005, vol. 140, no. 5, pp. 483–485.
Massé, K. and Dale, N., Purines as potential morphogens during embryonic development, Purinergic Signal, 2012, vol. 8, no. 3, pp. 503–521.
Bogdanov, Y., Rubino, A., and Burnstock, G., Characterisation of subtypes of the P2X and P2Y families of ATP receptors in the foetal human heart, Life Sci., 1998, vol. 62, no. 8, pp. 697–703.
Buvinic, S., Briones, R., and Huidobro-Toro, J.P., P2Y(1) and P2Y(2) receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed, Br. J. Pharmacol., 2002, vol. 136, no. 6, pp. 847–856.
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Original Russian Text © K.B. Pustovit, V.M. Potekhina, N.V. Pakhomov, V.S. Kuzmin, 2018, published in Vestnik Moskovskogo Universiteta, Seriya 16: Biologiya, 2018, Vol. 73, No. 1, pp. 52–59.
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Pustovit, K.B., Potekhina, V.M., Pakhomov, N.V. et al. Effects of Extracellular Diadenosine Tetraphosphate on Action Potentials in the Atrial and Ventricular Myocardium of the Rat Heart during Early Postnatal Ontogenesis. Moscow Univ. Biol.Sci. Bull. 73, 43–49 (2018). https://doi.org/10.3103/S0096392518010078
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DOI: https://doi.org/10.3103/S0096392518010078