About this project
This research area is highlighting on specific mechanisms underlying coagulation factor IIa (thrombin)-induced platelet activation. Much attention has been addressed towards the relative role played by the thrombin receptor subtypes designated PAR1 and PAR4. These receptors are co-expressed on the surface of platelets, share the same ligand and initiate identical signal transduction pathways. Current working hypothesis is that there must be physiological reasons for receptor co-expression and differences should be possible to discover. Our recent findings describe the mechanism behind PAR1 desensitization and subsequent “re-sensitization”. In sharp contrast to PAR1, the receptor PAR4 lacks the ability of undergoing receptor desensitization. On the other hand, PAR4 signaling rapidly normalize platelet responsiveness to PAR1 activation. Co-expression may thus be crucial in maintaining thrombin receptors in active states. Furthermore, we also found that the well-known cross-talk between the stress hormone adrenaline and thrombin is highly dependent on PAR4 but not PAR1. This implies that PAR4 may be more significant in platelet activation associated with pathophysiological stress reactions.