| Autor: |
Akihiro Okamura, Junichiro Miake, Takuya Tomomori, Aiko Takami, Tatsuya Sawano, Masaru Kato, Kazuyoshi Ogura, Daiki Tsujimoto, Shunsuke Kawatani, Kurniawan Priyono Agung, Tomomi Notsu, Ichiro Hisatome, Kazuhiro Yamamoto, Takeshi Imamura |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 148, Iss 4, Pp 351-357 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2022.02.001 |
| Popis: |
Endothelial nitric oxide synthase (eNOS) is a critical regulatory enzyme that controls vascular tone via the production of nitric oxide. Although thrombin also modulates vascular tone predominantly via the activation of protease-activated receptors (PARs), the time course and mechanisms involved in how thrombin controls eNOS enzymatic activity are unknown. eNOS enzymatic activity is enhanced by the phosphorylation of eNOS-Ser1177 and reduced by the phosphorylation of eNOS-Thr495. In this study, we hypothesized that thrombin regulates vascular tone through the differential phosphorylation of eNOS. Using rat descending aorta, we show that thrombin modulates vascular tone in an eNOS-dependent manner via activated PAR-1. We also show that thrombin causes a temporal biphasic response. Protein kinase C (PKC) is associated with second phase of thrombin-induced response. Western blot analysis demonstrated thrombin phosphorylated eNOS-Ser1177 and eNOS-Thr495 in human umbilical vein endothelial cells. A PKC inhibitor suppressed the thrombin-induced phosphorylation of eNOS-Thr495, but not that of eNOS-Ser1177. Our results suggest that thrombin induces a temporal biphasic vascular response through the differential phosphorylation of eNOS via activated PAR-1. Thrombin causes transient vasorelaxation by the phosphorylation of eNOS-Ser1177, and subsequent attenuation of vasorelaxation by the phosphorylation of eNOS-Thr495 via PKC, leading to the modulation of vascular tone. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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