Published online before print April 5, 2004, doi: 10.1161/01.hyp.0000126110.46402.dd
(Hypertension. 2004;43:1055.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Endogenous Diadenosine Tetraphosphate, Diadenosine Pentaphosphate, and Diadenosine Hexaphosphate in Human Myocardial Tissue
From Medizinische Klinik IV (J.L., V.J., N.G., W.Z., H.S., J.J.), Charite-Campus Benjamin Franklin, Berlin, Germany, and Institut für Pharmakologie und Toxikologie (J.N., W.S.), Universität Münster, Germany. J.L. is currently at the Institute für Anatomie, Klinikum der Friedrich Schiller Universität Jena, Germany.
Correspondence to Dr J. Jankowski, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail Joachim.Jankowski{at}charite.de
Diadenosine polyphosphates have been characterized as extracellular mediators controlling numerous physiological effects. In this study, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were isolated and identified in human myocardial tissue. Human myocardial tissue was homogenized and fractionated by affinity chromatography, displacement chromatography, anion-exchange chromatography, and reversed-phase chromatography. In fractions purified to homogeneity, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were revealed by matrix-assisted laser desorption/ionization mass spectrometry and ultraviolet spectroscopy. These diadenosine polyphosphates were further identified by enzymatic analysis, which demonstrated an interconnection of the phosphate groups with the adenosines in the 5' positions of the riboses. Furthermore, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were found in human cardiac-specific granules, and the amount of diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate was estimated in the range of 
500 µmol/L. In conclusion, the experiments show that the diadenosine polyphosphates with 2 and 3 phosphate groups occur in human myocardial tissue, and so do the diadenosine polyphosphates with 4 to 6 phosphate groups. After being released by cholinergic stimulation, which is known to affect diadenosine polyphosphate release from secretory granules, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate activate P2X purinoceptors in vascular smooth muscle; hence, they can act as vasoconstrictors. It may be inferred that the differential action of both predominantly vasodilator and vasoconstrictor diadenosine polyphosphates allow a fine-tuning of myocardial blood flow by locally released diadenosine polyphosphates.
Key Words: myocardium • cardiac function