Identification and characterization of adenosine 5'-tetraphosphate in human myocardial tissue
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Identification and characterization of adenosine 5'-tetraphosphate in human myocardial tissue. / Westhoff, Timm; Jankowski, Joachim; Schmidt, Sven; Luo, Jiankai; Giebing, Günter; Schlüter, Hartmut; Tepel, Martin; Zidek, Walter; van der Giet, Markus.
In: J BIOL CHEM, Vol. 278, No. 20, 16.05.2003, p. 17735-40.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Identification and characterization of adenosine 5'-tetraphosphate in human myocardial tissue
AU - Westhoff, Timm
AU - Jankowski, Joachim
AU - Schmidt, Sven
AU - Luo, Jiankai
AU - Giebing, Günter
AU - Schlüter, Hartmut
AU - Tepel, Martin
AU - Zidek, Walter
AU - van der Giet, Markus
PY - 2003/5/16
Y1 - 2003/5/16
N2 - Endocrine functions of the human heart have been studied extensively. Only recently, nucleotidergic mechanisms have been studied in detail. Therefore, an isolation strategy was developed to isolate novel nucleotide compounds from human myocardium. The human myocardial tissue was fractionated by several chromatographic studies. A substance purified to homogeneity was identified as adenosine 5'-tetraphosphate (Ap(4)) by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS), post-source decay MALDI MS, and enzymatic cleavage analysis. Furthermore, Ap(4) was also identified in ventricular specific granules. In the isolated perfused rat heart, Ap(4) elicited dose-dependent vasodilations. Vasodilator responses were abolished in the presence of the P(2Y1) receptor antagonist MRS 2179 (1 microm) or the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (50 microm). After removal of the endothelium by Triton X-100, Ap(4) induced dose-dependent vasoconstrictions. Inhibition of P(2X) receptors by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (30 microm) or desensitization of P(2X) receptors by alpha,beta-methylene ATP (alpha,beta-meATP, 1 microm) diminished these vasoconstrictor responses completely. In the present study Ap(4) has been isolated from human tissue. Ap(4) was shown to exist in human myocardial tissue and was identified in ventricular specific granules. In coronary vasculature the nucleotide exerted vasodilation via endothelial P(2Y1) receptors and vasoconstriction via P(2X) receptors on vascular smooth muscle cells. Ap(4) acts as an endogenous extracellular mediator and might contribute to the regulation of coronary perfusion.
AB - Endocrine functions of the human heart have been studied extensively. Only recently, nucleotidergic mechanisms have been studied in detail. Therefore, an isolation strategy was developed to isolate novel nucleotide compounds from human myocardium. The human myocardial tissue was fractionated by several chromatographic studies. A substance purified to homogeneity was identified as adenosine 5'-tetraphosphate (Ap(4)) by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS), post-source decay MALDI MS, and enzymatic cleavage analysis. Furthermore, Ap(4) was also identified in ventricular specific granules. In the isolated perfused rat heart, Ap(4) elicited dose-dependent vasodilations. Vasodilator responses were abolished in the presence of the P(2Y1) receptor antagonist MRS 2179 (1 microm) or the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (50 microm). After removal of the endothelium by Triton X-100, Ap(4) induced dose-dependent vasoconstrictions. Inhibition of P(2X) receptors by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (30 microm) or desensitization of P(2X) receptors by alpha,beta-methylene ATP (alpha,beta-meATP, 1 microm) diminished these vasoconstrictor responses completely. In the present study Ap(4) has been isolated from human tissue. Ap(4) was shown to exist in human myocardial tissue and was identified in ventricular specific granules. In coronary vasculature the nucleotide exerted vasodilation via endothelial P(2Y1) receptors and vasoconstriction via P(2X) receptors on vascular smooth muscle cells. Ap(4) acts as an endogenous extracellular mediator and might contribute to the regulation of coronary perfusion.
KW - Adenine Nucleotides
KW - Animals
KW - Detergents
KW - Endothelium, Vascular
KW - Humans
KW - Male
KW - Myocardium
KW - Octoxynol
KW - Perfusion
KW - Rats
KW - Rats, Inbred WKY
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
KW - Swine
KW - Time Factors
KW - Ultraviolet Rays
KW - Vasoconstrictor Agents
KW - Journal Article
U2 - 10.1074/jbc.M300288200
DO - 10.1074/jbc.M300288200
M3 - SCORING: Journal article
C2 - 12609994
VL - 278
SP - 17735
EP - 17740
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 20
ER -