PMID- 14515192 OWN - NLM STAT- MEDLINE DCOM- 20040706 LR - 20091119 IS - 0340-6245 (Print) IS - 0340-6245 (Linking) VI - 90 IP - 4 DP - 2003 Oct TI - Evidence for functionally active protease-activated receptor-3 (PAR-3) in human vascular smooth muscle cells. PG - 704-9 AB - 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. FAU - Bretschneider, Ellen AU - Bretschneider E AD - Institut fur Vaskulare Medizin Erfurt, Friedrich-Schiller-Universitat Jena, Erfurt, Germany. bretschn@zmkh.ef.uni-jena.de FAU - Spanbroek, Rainer AU - Spanbroek R FAU - Lotzer, Katharina AU - Lotzer K FAU - Habenicht, Andreas Johann Richard AU - Habenicht AJ FAU - Schror, Karsten AU - Schror K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Thromb Haemost JT - Thrombosis and haemostasis JID - 7608063 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Thrombin) RN - 0 (protease-activated receptor 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.21.5 (Thrombin) SB - IM MH - Calcium Signaling MH - DNA Replication/drug effects MH - Humans MH - Kinetics MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinases/metabolism MH - Muscle, Smooth, Vascular/chemistry/*cytology MH - Myocytes, Smooth Muscle/*chemistry MH - RNA, Messenger/analysis/drug effects MH - Receptors, Thrombin/*analysis/genetics/physiology MH - Saphenous Vein MH - Thrombin/pharmacology EDAT- 2003/09/30 05:00 MHDA- 2004/07/09 05:00 CRDT- 2003/09/30 05:00 PHST- 2003/09/30 05:00 [pubmed] PHST- 2004/07/09 05:00 [medline] PHST- 2003/09/30 05:00 [entrez] AID - 03100704 [pii] AID - 10.1160/TH03-04-0203 [doi] PST - ppublish SO - Thromb Haemost. 2003 Oct;90(4):704-9. doi: 10.1160/TH03-04-0203.