Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation
Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation
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DOI：
10.1038/sj.bjp.0706717
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发表时间：
2006-05-01
影响因子：
7.3
通讯作者：
Nasu, Tetsuyuki
中科院分区：
文献类型：
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作者：
Sato, Koichi;Ninomiya, Hiromichi;Nasu, Tetsuyuki
1蛋白酶激活受体（PAR）-2在肠道炎症反应中起重要作用。PAR-2介导的平滑肌功能的变化可能在病理生理学上导致炎症性肠病（IBD）中经常观察到的肠动力障碍。2正常大鼠结肠平滑肌中，胰蛋白酶诱导的卡巴胆碱和KCl诱导的收缩松弛对PAR-2的刺激可通过apamin组织预处理完全解决，但不能通过l-NMMA或神经元阻滞剂混合物预处理解决（河豚毒素、六烃季铵和普萘洛尔）。3在葡聚糖硫酸钠（DSS）引起的结肠炎症中，胰蛋白酶诱导的抑制作用显著降低。在DSS处理的大鼠结肠中，SLIGRL-NH 2（一种选择性PAR-2激活肽）诱导的舒张也减少。然而，1-乙基苯并咪唑啉-2-酮（一种小电导Ca 2+激活的K+通道的激活剂）的抑制作用不受影响。4 DSS处理大鼠结肠外肌层中PAR-2 mRNA的表达显著低于对照大鼠。5这些结果表明，在该实验性结肠炎大鼠模型中，结肠平滑肌中PAR-2介导的舒张系统受到抑制，并可能导致IBD中的运动障碍。
1 Protease-activated receptor (PAR)-2 plays important roles in intestinal inflammatory responses. Changes in PAR-2-mediated smooth muscle function may contribute pathophysiologically to the intestinal motility disorders often observed in inflammatory bowel disease (IBD).2 Stimulation of PAR-2 by trypsin-induced relaxation of carbachol- and KCl-induced contractions in normal rat colonic smooth muscle was completely resolved by tissue pretreatment with apamin, but not by pretreatment with l-NMMA or a cocktail of neuronal blockers (tetrodotoxin, hexamethonium and propranolol).3 In colon inflamed by dextran sodium sulphate (DSS), trypsin-induced inhibitory effects were significantly reduced. Relaxation induced by SLIGRL-NH2, a selective PAR-2-activating peptide, was also reduced in DSS-treated rat colon. However, inhibitory effects of 1-ethylbenzimidazolin-2-one, an activator of small conductance Ca2+-activated K+ channel, were unaffected.4 Expression of PAR-2 mRNA in colonic muscularis externa was significantly lower in DSS-treated rats than in control rats.5 These results suggest that the PAR-2 mediated relaxation system in colonic smooth muscle is suppressed in this experimental colitis rat model, and may contribute to motility disorders in IBD.