In the past several years, the identification of the human thrombin receptor has permitted considerable progress to be made in the understanding of the ways in which thrombin activates cells. To date, only a single receptor for thrombin has been identified: a member of the G protein-coupled family of receptors that has proved to be a proteolytic substrate for thrombin. Cleavage of the receptor enables it to activate, but also leaves it in a state in which it is unable to respond to thrombin a second time. This review examines the variety of cellular response mechanisms to thrombin, and the growing evidence for diversity among cells in the processes that remove and replace cleaved thrombin receptors, issues that are central to the development of therapeutically useful thrombin receptor antagonists.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/1050-1738(95)00051-A | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inflammation and Coagulation in Neurologic and Psychiatric Disorders.
Semin Thromb Hemost
January 2025
Department of Neurology, Sheba Medical Center, Tel Ha'Shomer, Israel.
Coagulation factors are intrinsically expressed in various brain cells, including astrocytes and microglia. Their interaction with the inflammatory system is important for the well-being of the brain, but they are also crucial in the development of many diseases in the brain such as stroke and traumatic brain injury. The cellular effects of coagulation are mediated mainly by protease-activated receptors.
View Article and Find Full Text PDFExosite crosstalk in thrombin.
J Thromb Haemost
January 2025
Department of Medicine, McMaster University; Department of Biochemistry and Biomedical Sciences, McMaster University; Thrombosis and Atherosclerosis Research Institute, McMaster University and Hamilton Health Sciences.
Thrombin is the central mediator of hemostasis, where it converts fibrinogen to fibrin, activates upstream factors to promote coagulation, activates factor XIII and thrombin-activatable fibrinolysis inhibitor to stabilize fibrin, mediates anticoagulation, and modulates cellular activity via cell surface receptors. Thus, regulation of thrombin activity is essential to the hemostatic balance. Thrombin is regulated by positively charged surface domains that surround the active site.
View Article and Find Full Text PDFProtease-activated receptor 1 in the pathogenesis of cystic fibrosis.
BMJ Open Respir Res
January 2025
Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Background: The most common cause of death in those with cystic fibrosis (CF) is respiratory failure due to bronchiectasis resulting from repeated cycles of respiratory infection and inflammation. Protease-activated receptor 1 (PAR1) is a cell surface receptor activated by serine proteases including neutrophil elastase, which is recognised as a potent modulator of inflammation. While PAR1 is known to play an important role in regulating inflammation, nothing is known about any potential role of this receptor in CF pathogenesis.
View Article and Find Full Text PDFThrombin-induced kynurenine 3-monooxygenase causes variations in the kynurenine pathway, leading to neurological deficits in a murine intracerebral hemorrhage model.
J Pharmacol Sci
February 2025
Department of Physical Chemistry for Bioactive Molecules, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
The purpose of the present study is to investigate changes in the kynurenine pathway after intracerebral hemorrhage (ICH) and its effects on ICH-induced injury. The exposure of a primary rat microglial culture to thrombin increased the mRNA level of kynurenine 3-monooxygenase (KMO), and this increase was attenuated by a p38 MAPK inhibitor. Thrombin also increased the protein level of KMO.
View Article and Find Full Text PDFChemotherapy alters thrombomodulin and factor VIIIc expression resulting in acquired activated protein C resistance and enhanced thrombin generation in cancer associated thrombosis.
Thromb Res
February 2025
Department of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Dublin, Ireland. Electronic address:
Background: Tumour type, treatment and patient related factors contribute to cancer associated venous thromboembolism (VTE), however, the role of each factor and the mechanisms involved are not understood.
Aim: To assess the role of the tumour, and of chemotherapy, in mediating the procoagulant response associated with VTE in gynaecological cancer patients.
Methods: Gynaecological cancer patients who developed VTE during follow-up (n = 59) (VTE+) were matched with treatment naïve(treatment (-)(VTE-)(n = 120) and chemotherapy treated patients(treatment (+)(VTE-) (n = 57)).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!