Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon
Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon
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DOI：
10.1038/sj.bjp.0704746
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发表时间：
2002-06-01
影响因子：
7.3
通讯作者：
Cerra, MC
中科院分区：
文献类型：
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作者：
Mulè, F;Baffi, MC;Cerra, MC
1 本研究检查了蛋白酶激活受体 (PAR)-1 和 PAR-2 的激动剂酶和受体激活肽对大鼠离体结肠节段的纵向和环状肌肉的机械效应，试图阐明 PAR 在肠道运动中的功能作用。2 通过同时记录腔内压力（环状肌肉活动指数）和等长张力（纵向肌肉活动指数）的变化，在体外检查对 PAR-1 和 PAR-2 激活的反应。3 PAR-1 激动剂、凝血酶 (0.1 nM - 3 muM) 和 SFLLRN-NH2 (1 nM - 3 muM) 以及 PAR-2 激动剂、胰蛋白酶 (0.1 nM - 10 muM) 和 SLIGRL-NH2 (1 nM - 10 muM) 在两个肌肉层中诱导不同的作用：环状肌自发收缩的减少和收缩效应或纵向肌肉中双相，先松弛后收缩，具体取决于浓度。4 apamin (0.1 muM) 大大降低或消除了抑制作用，表明它们主要通过激活 Ca2+ 依赖性小电导 K+ 通道而发生。5 对 PAR-1 和 PAR-2 的反应不受河豚毒素 (1 muM) 或吲哚美辛 (1 muM) 影响，表明它们是环加氧酶的独立副产物6 这些发现表明 PAR-1 和 PAR-2 在大鼠结肠中都有功能性表达。 PAR 介导纵向和环状肌肉机械活动的变化，这可能解释炎症条件下观察到的结肠运动的变化。
1 The present study examined the mechanical effects of agonist enzymes and receptor-activating peptides for protease-activated receptor (PAR)-1 and PAR-2 on longitudinal and circular muscle of rat isolated colonic segments in the attempt to clarify the PAR functional role in intestinal motility.2 The responses to PAR-1 and PAR-2 activation were examined in vitro by recording simultaneously the changes of endoluminal pressure (index of circular muscle activity) and of isometric tension (index of longitudinal muscle activity).3 Both PAR-1 agonists, thrombin (0.1 nM - 3 muM) and SFLLRN-NH2 (1 nM - 3 muM), and PAR-2 agonists, trypsin (0.1 nM - 10 muM) and SLIGRL-NH2 (1 nM - 10 muM), induced different effects in the two muscular layers: a reduction of the spontaneous contractions in the circular muscle and a contractile effect or biphasic, relaxation followed by contraction, depending on the concentration, in the longitudinal muscle.4 The inhibitory effects were greatly reduced or abolished by apamin (0.1 muM) indicating that they mainly occur via activation of Ca2+-dependent small conductance, K+-channels.5 The responses to PAR-1 and PAR-2 were unaffected by tetrodotoxin (1 muM) or indomethacin (1 muM) suggesting that are independent by products of cyclooxygenase or by neural action potentials.6 These findings indicate that both PAR-1 and PAR-2 are functionally expressed in rat colon. PARs mediate changes of the mechanical activity of longitudinal and circular muscle which might explain the alterations of colonic motility observed during inflammatory conditions.