Identification and Characterization of Adenosine 5′-Tetraphosphate in Human Myocardial Tissue
| Autor: | Hartmut Schlüter, Timm H. Westhoff, Martin Tepel, Sven Schmidt, Jiankai Luo, Joachim Jankowski, Walter Zidek, Markus van der Giet, G. Giebing |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Vascular smooth muscle Endothelium Octoxynol Swine Ultraviolet Rays medicine.drug_class Detergents Vasodilation Biology Rats Inbred WKY Biochemistry Internal medicine Extracellular medicine Animals Humans Vasoconstrictor Agents Receptor Molecular Biology Adenine Nucleotides Myocardium Cell Biology Receptor antagonist Molecular biology Adenosine Rats Perfusion medicine.anatomical_structure Endocrinology Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Endothelium Vascular medicine.symptom Vasoconstriction medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 278:17735-17740 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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