Study on roles for PAR-2, a G protein-coupled receptor, in acute inflammation

蛋白酶激活受体（protease-activated receptor，PAR）是一个G蛋白偶联受体家族，由4个成员组成，在炎症、组织损伤和出血时激活，调节多种生理功能。本研究首先研究了脂多糖处理小鼠唾液腺中PAR-2敏感性的变化，发现在全身炎症条件下，内源性PAR-2激活剂可使PAR-2紧张性激活和脱敏。内源性PAR激活剂包括凝血酶、因子VII和因子X、肥大细胞类胰蛋白酶可能在感染性休克中被激活和/或进入组织。这些酶通过PAR激活引起的血管舒张可能有助于脓毒性休克引起的低血压的发展。在这种情况下，我们研究了潜在的PAR激活引起的血管收缩和舒张的机制。然后，我们研究了PAR的作用，已知存在于辣椒素敏感的感觉神经元，炎症内脏痛和腮腺炎相关的疼痛。我们的数据提供了新的证据，PAR，特别是PAR-2，参与炎症和相关的疼痛，循环障碍等。

The protease-activated receptor(PAR), a G protein-coupled receptor family consists of 4 members, and modulates a variety of physiological functions upon activation in response to inflammation, tissue injury and hemorrhage. The present study investigated the roles and changes of PARs, particularly PAR-2, in acute inflammation.We first studied changes of sensitivity of PAR-2 present in the salivary glands in mice treated with lipopolysaocharide, and found that PAR-2 might be tonically activated and desensitized by endogenous PAR-2 activators under systemic inflammatory conditions. Endogenous PAR activators including thrombin, factors VII and X, mast cell tryptase might become activated and/or accessible to tissues in septic shock. Vasodilation by these enzymes via PAR activation might contribute to development of hypotension caused by septic shock. In this context, we examined the mechanisms underlying the vascular contraction and relaxation caused by PAR activation. We then investigated roles of PARs, known to be present in capsaicin-sensitive sensory neurons, in inflammatory visceral pain and parotitis-related pain. Our data provide novel evidence that PARs, particularly PAR-2,is involved in inflammation and related pain, circulatory disturbance, etc.