ISSN:
1573-9023
Keywords:
Thrombosis
;
Restenosis
;
Inflammation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Summary A G-protein-coupled thrombin receptor has been identified, cloned and shown to be present on platelets, endothelial cells, fibroblasts and vascular smooth muscle cells. α-Thrombin binds to this receptor via thrombin's anion-binding exosite and catalyzes exposure of a new NH2-terminus. The new receptor NH2-terminus acts as an agonistic ‘tethered ligand’ that comprises part of the receptor it activates. The first five or more amino acids of the new NH2-terminus (beginning with SFLLR in the human receptor) can directly activate the receptor in the absence of thrombin. Because thrombin receptor activation may participate in thrombosis, inflammation and fibroproliferative disorders, research is being conducted on several strategies that might interfere with the receptor-mediated pathophysiologic actions of thrombin. The structure-activity relationship for thrombin receptor agonist peptides has been studied in detail, and some general requirements for agonist activity have emerged. Although several peptide-based thrombin receptor antagonists have been described, these earliest examples are not very potent and they appear to be partial agonists in cells other than platelets. Despite the limitations of these prototypes, initial studies with such compounds have demonstrated the importance of this thrombin receptor in α-thrombin-mediated activation of platelets and certain other cells and in arterial thrombosis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02171864
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