Evidence for functionally active protease-activated receptor-3 (PAR-3) in human vascular smooth muscle cells

Thromb Haemost. 2003 Oct;90(4):704-9. doi: 10.1160/TH03-04-0203.


The present study investigates whether vascular smooth muscle cells of the human saphenous vein (SMC) express a functionally active protease-activated receptor-3 (PAR-3). PAR-3 mRNA was detected by RT-PCR. In the presence of thrombin, a rapid and transient increase in PAR-3 mRNA was observed. Stimulation of SMC with thrombin or the synthetic PAR-3-activating peptide, TFRGAP, resulted in transient mobilization of intracellular calcium. After a preceding challenge with thrombin, the calcium signal to TFRGAP was abolished, suggesting cleavage and subsequent desensitization of PAR-3 by thrombin. Activation of PAR-3 by TFRGAP elicited a time-dependent activation of the extracellular-signal-regulated kinase (ERK)-1/2 with a maximum response 10-20 min after stimulation. At 200 microM, TFRGAP increased [3H]-thymidine incorporation into cellular DNA about two-fold. These data indicate that PAR-3 is expressed in human SMC and triggers intracellular signaling. Thus, in the SMC PAR-3 might contribute to thrombin-induced responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Signaling
  • DNA Replication / drug effects
  • Humans
  • Kinetics
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth, Vascular / chemistry
  • Muscle, Smooth, Vascular / cytology*
  • Myocytes, Smooth Muscle / chemistry*
  • RNA, Messenger / analysis
  • RNA, Messenger / drug effects
  • Receptors, Thrombin / analysis*
  • Receptors, Thrombin / genetics
  • Receptors, Thrombin / physiology
  • Saphenous Vein
  • Thrombin / pharmacology


  • RNA, Messenger
  • Receptors, Thrombin
  • protease-activated receptor 3
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Thrombin