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

Ellen Bretschneider; Rainer Spanbroek; Katharina Lötzer; Andreas Johann Richard Habenicht; Karsten Schrör

doi:10.1160/TH03-04-0203

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(04): 704-709
DOI: 10.1160/TH03-04-0203

Vascular Development and Vessel Remodeling

Schattauer GmbH

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

Ellen Bretschneider

¹Institut für Vaskuläre Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Rainer Spanbroek

¹Institut für Vaskuläre Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Katharina Lötzer

¹Institut für Vaskuläre Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Andreas Johann Richard Habenicht

¹Institut für Vaskuläre Medizin Erfurt, Friedrich-Schiller-Universität Jena, Germany

,

Karsten Schrör

²Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany

› Author Affiliations

Abstract

Summary

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 µM, 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.

Keywords

Vascular smooth muscle cells - protease-activated receptor-3 - signaling

Full Text

References

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