Nguyen Cathy, Coelho Anne-Marie, Grady Eileen, Compton Steven J, Wallace John L, Hollenberg Morley D, Cenac Nicolas, Garcia-Villar Rafael, Bueno Lionel, Steinhoff Martin, Bunnett Nigel W, Vergnolle Nathalie
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Can J Physiol Pharmacol. 2003 Sep;81(9):920-7. doi: 10.1139/y03-080.
Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR2 agonists administered intracolonically in mice induce inflammation via a neurogenic mechanism. Pretreatment of mice with neurokinin-1 and calcitonin-gene-related peptide (CGRP) receptor antagonists or with capsaicin showed attenuated PAR2-agonist-induced colitis. Immunohistochemistry demonstrated a differential expression of a marker for the type-1 CGRP receptor during the time course of PAR2-agonist-induced colitis, further suggesting a role for CGRP. We conclude that PAR2-agonist-induced intestinal inflammation involves the release of neuropeptides, which by acting on their receptors cause inflammation. These results implicate PAR2 as an important mediator of intestinal neurogenic inflammation.
蛋白酶激活受体-2（PAR2）的激活通过未知机制诱导结肠炎症。我们推测，向小鼠结肠内给药PAR2激动剂会通过神经源性机制诱发炎症。用神经激肽-1和降钙素基因相关肽（CGRP）受体拮抗剂或辣椒素预处理小鼠后，PAR2激动剂诱导的结肠炎有所减轻。免疫组织化学显示，在PAR2激动剂诱导的结肠炎病程中，1型CGRP受体标志物表达存在差异，进一步表明CGRP发挥了作用。我们得出结论，PAR2激动剂诱导的肠道炎症涉及神经肽的释放，神经肽通过作用于其受体引发炎症。这些结果表明PAR2是肠道神经源性炎症的重要介质。
