Uridine adenosine tetraphosphate
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Uridine adenosine tetraphosphate : a novel endothelium- derived vasoconstrictive factor. / Jankowski, Vera; Tölle, Markus; Vanholder, Raymond; Schönfelder, Gilbert; van der Giet, Markus; Henning, Lars; Schlüter, Hartmut; Paul, Martin; Zidek, Walter; Jankowski, Joachim.
In: NAT MED, Vol. 11, No. 2, 02.2005, p. 223-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Uridine adenosine tetraphosphate
T2 - a novel endothelium- derived vasoconstrictive factor
AU - Jankowski, Vera
AU - Tölle, Markus
AU - Vanholder, Raymond
AU - Schönfelder, Gilbert
AU - van der Giet, Markus
AU - Henning, Lars
AU - Schlüter, Hartmut
AU - Paul, Martin
AU - Zidek, Walter
AU - Jankowski, Joachim
PY - 2005/2
Y1 - 2005/2
N2 - Beyond serving as a mechanical barrier, the endothelium has important regulatory functions. The discovery of nitric oxide revolutionized our understanding of vasoregulation. In contrast, the identity of endothelium-derived vasoconstrictive factors (EDCFs) remains unclear. The supernatant obtained from mechanically stimulated human endothelial cells obtained from dermal vessels elicited a vasoconstrictive response in an isolated perfused rat kidney. A purinoceptor blocker had a greater effect than an endothelin receptor blocker in decreasing endothelially derived vasoconstriction in the isolated perfused rat kidney. The nucleotide uridine adenosine tetraphosphate (Up(4)A) was isolated from the supernatant of stimulated human endothelium and identified by mass spectrometry. Up(4)A is likely to exert vasoconstriction predominantly through P2X1 receptors, and probably also through P2Y2 and P2Y4 receptors. Plasma concentrations of Up(4)A that cause vasoconstriction are found in healthy subjects. Stimulation with adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP), acetylcholine, endothelin, A23187 and mechanical stress releases Up(4)A from endothelium, suggesting that Up(4)A contributes to vascular autoregulation. To our knowledge, Up(4)A is the first dinucleotide isolated from living organisms that contains both purine and pyrimidine moieties. We conclude that Up(4)A is a novel potent nonpeptidic EDCF. Its vasoactive effects, plasma concentrations and its release upon endothelial stimulation strongly suggest that Up(4)A has a functional vasoregulatory role.
AB - Beyond serving as a mechanical barrier, the endothelium has important regulatory functions. The discovery of nitric oxide revolutionized our understanding of vasoregulation. In contrast, the identity of endothelium-derived vasoconstrictive factors (EDCFs) remains unclear. The supernatant obtained from mechanically stimulated human endothelial cells obtained from dermal vessels elicited a vasoconstrictive response in an isolated perfused rat kidney. A purinoceptor blocker had a greater effect than an endothelin receptor blocker in decreasing endothelially derived vasoconstriction in the isolated perfused rat kidney. The nucleotide uridine adenosine tetraphosphate (Up(4)A) was isolated from the supernatant of stimulated human endothelium and identified by mass spectrometry. Up(4)A is likely to exert vasoconstriction predominantly through P2X1 receptors, and probably also through P2Y2 and P2Y4 receptors. Plasma concentrations of Up(4)A that cause vasoconstriction are found in healthy subjects. Stimulation with adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP), acetylcholine, endothelin, A23187 and mechanical stress releases Up(4)A from endothelium, suggesting that Up(4)A contributes to vascular autoregulation. To our knowledge, Up(4)A is the first dinucleotide isolated from living organisms that contains both purine and pyrimidine moieties. We conclude that Up(4)A is a novel potent nonpeptidic EDCF. Its vasoactive effects, plasma concentrations and its release upon endothelial stimulation strongly suggest that Up(4)A has a functional vasoregulatory role.
KW - Adenine Nucleotides
KW - Animals
KW - Cells, Cultured
KW - Endothelial Cells
KW - Endothelium, Vascular
KW - Humans
KW - In Vitro Techniques
KW - Kidney
KW - Mass Spectrometry
KW - Molecular Weight
KW - Rats
KW - Uracil Nucleotides
KW - Vasoconstrictor Agents
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/nm1188
DO - 10.1038/nm1188
M3 - SCORING: Journal article
C2 - 15665829
VL - 11
SP - 223
EP - 227
JO - NAT MED
JF - NAT MED
SN - 1078-8956
IS - 2
ER -