PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors.
PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors.
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DOI：
10.1152/ajpgi.00064.2003
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发表时间：
2003-10
期刊：
影响因子：
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通讯作者：
Aiping Zhao;T. Shea-Donohue
中科院分区：
文献类型：
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作者：
Aiping Zhao;T. Shea-Donohue
蛋白酶激活受体-2（PAR-2）是一种G蛋白偶联受体，在整个肠道中表达。PAR-2参与胃肠运动的调节是众所周知的，然而，结果是不一致的。本研究探讨PAR-2激活对离体小鼠小肠平滑肌功能的影响及其机制。胰蛋白酶和PAR-2激活肽SLIGRL诱导的一个小的放松，然后浓度依赖性收缩。对胰蛋白酶的敏感性大于对SLIGRL的敏感性（EC 50 = 0.03 vs. 40 microM），但最大响应相似（12.3 +/- 1.6 vs. 13.7 +/- 1.3 N/cm 2）。胰蛋白酶诱发的收缩（1 μ M）表现出快速脱敏，而脱敏的SLIGRL的反应是少，即使在高浓度（50 μ M）。阿托品对PAR-2激动剂诱导的收缩无影响。相比之下，TTX和辣椒素显着减弱这些收缩，暗示可能涉及辣椒素敏感的感觉神经的神经原性机制。此外，由胰蛋白酶和SLIGRL诱导的收缩被神经激肽受体NK 1拮抗剂SR-140333或NK 2拮抗剂SR-48968单独降低，或被SR-140333和SR-48968联合应用进一步降低，表明神经激肽受体的参与。此外，脱敏神经激肽受体与P物质和/或神经激肽A减少PAR-2激动剂诱发的收缩。我们得出结论，PAR-2激动剂诱导的收缩小鼠肠平滑肌，是由神经介导的。兴奋作用也依赖于感觉神经通路，需要NK 1和NK 2受体。
Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor and is expressed throughout the gut. It is well known that PAR-2 participates in the regulation of gastrointestinal motility; however, the results are inconsistent. The present study investigated the effect and mechanism of PAR-2 activation on murine small intestinal smooth muscle function in vitro. Both trypsin and PAR-2-activating peptide SLIGRL induced a small relaxation followed by a concentration-dependent contraction. The sensitivity to trypsin was greater than that to SLIGRL (EC50 = 0.03 vs. 40 microM), but maximal responses were similar (12.3 +/- 1.6 vs. 13.7 +/- 1.3 N/cm2). Trypsin-evoked contraction (1 microM) exhibited a rapid desensitization, whereas the desensitization of response to SLIGRL was less even at high concentration (50 microM). Atropine had no effect on PAR-2 agonist-induced contractions. In contrast, TTX and capsaicin significantly attenuated those contractions, implicating a neurogenic mechanism that may involve capsaicin-sensitive sensory nerves. Furthermore, contractions induced by trypsin and SLIGRL were reduced by neurokinin receptor NK1 antagonist SR-140333 or NK2 antagonist SR-48968 alone or were further reduced by combined application of SR-140333 and SR-48968, indicating the involvement of neurokinin receptors. In addition, desensitizing neurokinin receptors with substance P and/or neurokinin A decreased the PAR-2 agonist-evoked contraction. We concluded that PAR-2 agonists induced a contraction of murine intestinal smooth muscle that was mediated by nerves. The excitatory effect is also dependent on sensory neural pathways and requires both NK1 and NK2 receptors.