Endogenous diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate in human myocardial tissue
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Endogenous diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate in human myocardial tissue. / Luo, Jiankai; Jankowski, Vera; Güngär, Nihayrt; Neumann, Joachim; Schmitz, Wilhelm; Zidek, Walter; Schlüter, Hartmut; Jankowski, Joachim.
in: HYPERTENSION, Jahrgang 43, Nr. 5, 05.2004, S. 1055-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Endogenous diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate in human myocardial tissue
AU - Luo, Jiankai
AU - Jankowski, Vera
AU - Güngär, Nihayrt
AU - Neumann, Joachim
AU - Schmitz, Wilhelm
AU - Zidek, Walter
AU - Schlüter, Hartmut
AU - Jankowski, Joachim
PY - 2004/5
Y1 - 2004/5
N2 - 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 approximately 500 micromol/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.
AB - 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 approximately 500 micromol/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.
KW - Cholinergic Agents
KW - Chromatography, Affinity
KW - Chromatography, Gel
KW - Chromatography, High Pressure Liquid
KW - Chromatography, Ion Exchange
KW - Cytoplasmic Granules
KW - Dinucleoside Phosphates
KW - Heart
KW - Humans
KW - Myocardium
KW - Potassium Channels
KW - Receptors, Purinergic P2
KW - Receptors, Purinergic P2X
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
KW - Spectrophotometry, Ultraviolet
KW - Vasoconstriction
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1161/01.hyp.0000126110.46402.dd
DO - 10.1161/01.hyp.0000126110.46402.dd
M3 - SCORING: Journal article
C2 - 15066958
VL - 43
SP - 1055
EP - 1059
JO - HYPERTENSION
JF - HYPERTENSION
SN - 0194-911X
IS - 5
ER -