Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage
Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical role in the management of SAH patients. However, the mechanism of cerebral vasospasm still remains elusive, while effective therapeutic stra...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319313143 |
| _version_ | 1811261796032446464 |
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| author | Yasutoshi Kai Yoshihisa Maeda Tomio Sasaki Hideo Kanaide Katsuya Hirano |
| author_facet | Yasutoshi Kai Yoshihisa Maeda Tomio Sasaki Hideo Kanaide Katsuya Hirano |
| author_sort | Yasutoshi Kai |
| collection | DOAJ |
| description | Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical role in the management of SAH patients. However, the mechanism of cerebral vasospasm still remains elusive, while effective therapeutic strategies also remain to be established. The role of thrombin and its receptor proteinase-activated receptor 1 (PAR1) in cerebral vasospasm was investigated using a rabbit double hemorrhage SAH model. The expression of PAR1 was up-regulated and the contractile response to thrombin was markedly enhanced in the basilar artery of SAH models. The intrathecal administration of a PAR1 antagonist prevented the up-regulation of PAR1 and the enhancement of the contractile responses to thrombin in SAH. These observations thus suggest that PAR1 may play a pivotal role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin activates PAR1, thereby up-regulating the expression of PAR1, which culminates in the increased contractile response to thrombin in the basilar artery. PAR1 antagonists are thus anticipated to be a novel therapeutic strategy for cerebral vasospasm. However, further studies are needed before establishing the clinical usefulness of PAR1 antagonists. Keywords:: subarachnoid hemorrhage, cerebral vasospasm, thrombin, proteinase-activated receptor, 1 (PAR1), antagonist |
| first_indexed | 2024-04-12T19:12:19Z |
| format | Article |
| id | doaj.art-373560bc3c3d402caf20487b30288786 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T19:12:19Z |
| publishDate | 2008-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-373560bc3c3d402caf20487b302887862022-12-22T03:19:51ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011084426432Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid HemorrhageYasutoshi Kai0Yoshihisa Maeda1Tomio Sasaki2Hideo Kanaide3Katsuya Hirano4Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDivision of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; International University of Health and Welfare, Fukuoka 814-0001, JapanDivision of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Corresponding author. khirano@molcar.med.kyushu-u.ac.jpCerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical role in the management of SAH patients. However, the mechanism of cerebral vasospasm still remains elusive, while effective therapeutic strategies also remain to be established. The role of thrombin and its receptor proteinase-activated receptor 1 (PAR1) in cerebral vasospasm was investigated using a rabbit double hemorrhage SAH model. The expression of PAR1 was up-regulated and the contractile response to thrombin was markedly enhanced in the basilar artery of SAH models. The intrathecal administration of a PAR1 antagonist prevented the up-regulation of PAR1 and the enhancement of the contractile responses to thrombin in SAH. These observations thus suggest that PAR1 may play a pivotal role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin activates PAR1, thereby up-regulating the expression of PAR1, which culminates in the increased contractile response to thrombin in the basilar artery. PAR1 antagonists are thus anticipated to be a novel therapeutic strategy for cerebral vasospasm. However, further studies are needed before establishing the clinical usefulness of PAR1 antagonists. Keywords:: subarachnoid hemorrhage, cerebral vasospasm, thrombin, proteinase-activated receptor, 1 (PAR1), antagonisthttp://www.sciencedirect.com/science/article/pii/S1347861319313143 |
| spellingShingle | Yasutoshi Kai Yoshihisa Maeda Tomio Sasaki Hideo Kanaide Katsuya Hirano Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage Journal of Pharmacological Sciences |
| title | Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage |
| title_full | Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage |
| title_fullStr | Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage |
| title_full_unstemmed | Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage |
| title_short | Basic and Translational Research on Proteinase-Activated Receptors: The Role of Thrombin Receptor in Cerebral Vasospasm in Subarachnoid Hemorrhage |
| title_sort | basic and translational research on proteinase activated receptors the role of thrombin receptor in cerebral vasospasm in subarachnoid hemorrhage |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319313143 |
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