Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor
| Autor: | T. T. Andersen, Paul M. Vanhoutte, Rudi Busse, V. B. Schini-Kerth, John W. Fenton, Beate Fisslthaler |
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| Rok vydání: | 1995 |
| Předmět: |
Vascular smooth muscle
biology Hematology Nitric oxide Cell biology Nitric oxide synthase chemistry.chemical_compound medicine.anatomical_structure Thrombin chemistry Biochemistry Cell surface receptor Thrombin receptor medicine biology.protein Receptor circulatory and respiratory physiology Blood vessel medicine.drug |
| Zdroj: | Thrombosis and Haemostasis. 74:980-986 |
| ISSN: | 2567-689X 0340-6245 |
| DOI: | 10.1055/s-0038-1649859 |
| Popis: | Proteolytically active forms of thrombin ( alpha- and gamma-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 beta (IL-1 beta ) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-alpha-thrombin (PPACK-alpha-thrombin) and diisopropylphosphoryl-alpha-thrombin (DIP-alpha-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 beta-activated vascular smooth muscle cells or cells treated with IL-1 beta plus PPACK-alpha-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L-arginine. No relaxations were obtained with untreated cells or IL-1 beta-treated cells in the presence of alpha-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 beta was impaired by alpha-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells. |
| Databáze: | OpenAIRE |
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