Kinin B1Receptors Stimulate Nitric Oxide Production in Endothelial Cells: Signaling Pathways Activated by Angiotensin I-Converting Enzyme Inhibitors and Peptide Ligands
| العنوان: | Kinin B1Receptors Stimulate Nitric Oxide Production in Endothelial Cells: Signaling Pathways Activated by Angiotensin I-Converting Enzyme Inhibitors and Peptide Ligands |
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| المؤلفون: | Ervin G. Erdös, Sinisa Stanisavljevic, Tatjana Ignjatovic, Randal A. Skidgel, Viktor Brovkovych |
| المصدر: | Molecular Pharmacology. 66:1310-1316 |
| بيانات النشر: | American Society for Pharmacology & Experimental Therapeutics (ASPET), 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Cholera Toxin, medicine.medical_specialty, Enalaprilat, Bradykinin, Angiotensin-Converting Enzyme Inhibitors, Kinins, Pharmacology, Arginine, Ligands, Nitric Oxide, Receptor, Bradykinin B1, chemistry.chemical_compound, Internal medicine, medicine, Animals, Humans, Receptor, Protein Kinase C, biology, Chemistry, Kallidin, Angiotensin-converting enzyme, Kinin, Endocrinology, ACE inhibitor, biology.protein, Molecular Medicine, Calcium, Cattle, Endothelium, Vascular, Signal transduction, Peptides, Signal Transduction, medicine.drug |
| الوصف: | We reported previously a novel mode of action of angiotensin I-converting enzyme (kininase II; ACE) inhibitors mediated through the direct activation of bradykinin B(1) receptor, independent of endogenous kinins or ACE (J Biol Chem 277:16847-16852, 2002). We aimed to further clarify the mechanism of activation of B(1) receptor, which leads to prolonged nitric oxide (NO) release. The ACE inhibitor enalaprilat and the peptide ligand desArg(10)-kallidin (in nanomolar concentrations) release NO by activating endothelial NO synthase (eNOS) in bovine and inducible NO synthase (iNOS) in stimulated human endothelial cells. The peptide and the ACE inhibitor ligands activate eNOS by facilitating different signaling pathways. DesArg(10)-kallidin enhances inositol-phosphate generation and elevates [Ca(2+)](i) by first augmenting intracellular release and then the influx of extracellular Ca(2+). In contrast, enalaprilat stimulates only the influx of extracellular Ca(2+) through rare earth-sensitive channels, and its effect is blocked by cholera toxin or protein kinase C inhibitors. In addition, unlike desArg(10)-kallidin, enalaprilat can also release NO independent of Ca(2+) in bovine endothelial cells. The inflammatory cytokines interleukin-1beta and interferon-gamma induce both B(1) receptor and iNOS in human endothelial cells. In contrast to eNOS, B(1) ligands activate iNOS similarly. Both desArg(10)-kallidin and ACE inhibitors enhance arginine uptake and release NO independent of [Ca(2+)](i) elevation. This is the first report on the direct activation of B(1) receptor by ACE inhibitors in human endothelial cells. This interaction leads to prolonged NO release and possibly contributes to the documented benefits of the use of ACE inhibitors. |
| تدمد: | 1521-0111 0026-895X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8244b13a20646a81ffbb26eb2806e0baTest https://doi.org/10.1124/mol.104.001990Test |
| رقم الانضمام: | edsair.doi.dedup.....8244b13a20646a81ffbb26eb2806e0ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15210111 0026895X |
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