Adenosine 5'-tetraphosphate is a highly potent purinergic endothelium-derived vasoconstrictor
| Autor: | Tao Huang, Joachim Jankowski, Walter Zidek, Annette Wiedon, Markus Tölle, Joanna Kowalska, Markus van der Giet, Franziska Hub, Vera Jankowski, Andrzej Guranowski, Jacek Jemielity, Mirjam Schuchardt, Christoph Loddenkemper |
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| Rok vydání: | 2008 |
| Předmět: |
Purinergic P2 Receptor Agonists
medicine.medical_specialty Mean arterial pressure Endothelium Physiology Blood Pressure Kidney Peptides Cyclic Nitric oxide chemistry.chemical_compound In vivo Internal medicine medicine Animals Humans Vasoconstrictor Agents Antihypertensive Agents Cells Cultured Chemistry Adenine Nucleotides Receptors Purinergic P2 Purinergic receptor Endothelial Cells Adenosine Rats Endocrinology medicine.anatomical_structure Receptors Purinergic P2X Vasoconstriction sense organs medicine.symptom Cardiology and Cardiovascular Medicine Endothelin receptor medicine.drug |
| Zdroj: | Circulation research. 103(10) |
| ISSN: | 1524-4571 |
| Popis: | Besides 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 still remains uncertain. The supernatant from mechanically stimulated human microvascular endothelial cells elicited a potent vasoconstrictive response in the isolated perfused rat kidney. Whereas a nonselective purinoceptor blocker blocked this vasoactivity most potently, the inhibition of the endothelin receptor by BQ123 weakly affected that vasoconstrictive response. As a compound responsible for that vasoconstrictive effect, we have isolated from HMECs and identified the mononucleotide adenosine 5′-tetraphosphate (AP4). This nucleotide proved to be the most potent vasoactive purinergic mediator identified to date, exerting the vasoconstriction predominantly through activation of the P2X1 receptor. The intraarterial application of AP4 in a Wistar–Kyoto rat induced a strong increase of the mean arterial pressure. The plasma concentration of AP4 is in the nanomolar range, which, in vivo, induces a significant change in the mean arterial pressure. To our knowledge, AP4, which exerts vasoactive effects, is the most potent endogenous mononucleotide identified to date in mammals. The effects of AP4, the plasma concentration of AP4, and its release suggest that this compound functions as an important vasoregulator. |
| Databáze: | OpenAIRE |
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