PhD student Yonsei University Incheon, Inch'on-jikhalsi, Republic of Korea
Yunkyung Heo (Yonsei University)| Eunhee Yang (Yonsei University)| Wan Namkung (Yonsei University)
Protease-activated receptor 2 (PAR2), a G-protein-coupled receptor expressed in many cell types such as epithelial, endothelial, neuronal, immune and smooth muscle cells, plays an important role in various inflammatory diseases. Activated PAR2 stimulates complex intracellular signal transduction pathways via G-protein- and β-arrestin-mediated signaling. In this study, we serendipitously discovered that GB83, a known PAR2 antagonist, activated PAR2 and induced rapid desensitization of PAR2. GB83 increased intracellular calcium concentration only in HT29 cells expressing PAR2 but not in PAR2 knockout HT29 cells. AZ3451, a potent PAR2 antagonist, completely blocked the GB83-induced intracellular calcium elevation. In addition, GB83 strongly stimulated phosphorylation of ERK1/2 and p38 MAPK, and internalization of PAR2 in HT29 cells, which were all completely blocked by AZ3451. These results revealed that GB83 is a bona fide agonist of PAR2 which induces rapid desensitization and internalization of PAR2.