Coelho Anne-Marie, Ossovskaya Valeria, Bunnett Nigel W
Department of Surgery and Physiology, University of California San Francisco, San Francisco, California 94143-0660, USA.
Curr Med Chem Cardiovasc Hematol Agents. 2003 Mar;1(1):61-72. doi: 10.2174/1568016033356715.
Protease-activated receptor 2 (PAR2) is the second member of a new subfamily of G-protein coupled receptors: the protease-activated receptors (PARs). At present, four different PARs have been cloned and all of them share the same basic mechanism of activation. A serine protease cleaves the extended, extracellular N-terminus of the receptor at a specific site within the protein chain to expose an N-terminal tethered ligand domain, which binds to and activates the cleaved receptor. In this manner, trypsin and mast cell beta-tryptase activate PAR2. PARs are single use receptors because proteolytic activation is irreversible and the cleaved receptors are degraded in lysosomes. Thus, PARs play important roles in emergency situations, such as trauma and inflammation. Emerging evidence indicates that PAR2 is involved in the cardiovascular, pulmonary and gastrointestinal systems, where it controls inflammation and nociception. Work with selective agonists and knockout animals suggests a contribution of PAR2 to certain inflammatory diseases. Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases.
蛋白酶激活受体2（PAR2）是G蛋白偶联受体新亚家族——蛋白酶激活受体（PARs）的第二个成员。目前，已克隆出四种不同的PARs，它们都具有相同的基本激活机制。丝氨酸蛋白酶在蛋白质链内的特定位点切割受体延伸的细胞外N端，以暴露N端拴系配体结构域，该结构域与切割后的受体结合并激活它。通过这种方式，胰蛋白酶和肥大细胞β-胰蛋白酶激活PAR2。PARs是一次性受体，因为蛋白水解激活是不可逆的，且切割后的受体在溶酶体中降解。因此，PARs在创伤和炎症等紧急情况下发挥重要作用。新出现的证据表明，PAR2参与心血管、肺和胃肠道系统，在这些系统中它控制炎症和痛觉。对选择性激动剂和基因敲除动物的研究表明PAR2与某些炎症性疾病有关。因此，这些受体的选择性拮抗剂或激动剂可能是治疗人类疾病的有用治疗药物。
