Thrombin Receptor Agonist Peptide

Thrombin signaling of platelets is mediated by a G protein-coupled protease-activated receptor (PAR). The PAR is activated after thrombin binding and subsequent cleavage of the amino terminal end of the receptor. This new amino terminus acts as a tethered ligand and binds intramolecularly to the body of the PAR, resulting in a transmembrane signal. Synthetic thrombin receptor agonist peptides (TRAP) of 6 residues (SFLLRN) and 14 residues (SFLLRNPNDKYEPF), respectively corresponding to aa42-47 and aa42-55 of the human thrombin receptor were found to be as effective as thrombin for Ca2+ mobilization. It was also shown that these peptides are far less active on pig and guinea pig platelets, whereas completely inactive on rat and rabbit platelets.