Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats
Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats
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DOI：
10.1111/j.1365-2982.2005.00648.x
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发表时间：
2005-06-01
影响因子：
3.5
通讯作者：
Myers, DA
中科院分区：
文献类型：
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作者：
Greenwood-van Meerveld, B;Johnson, AC;Myers, DA
应激与肠易激综合征(IBS)症状学之间的潜在关系表明，应激中介激素，如促肾上腺皮质激素释放因子(CRF)，可能在IBS患者对刺激的感知改变中发挥作用。在以前的研究中，具有高度焦虑遗传指标的Wistar-京都(WKY)大鼠表现出结肠过敏，并伴随着中枢神经系统内高基础水平的CRF。在目前的研究中，我们测试了选择性的非肽CRF受体拮抗剂antalarmin将抑制WKY大鼠结肠超敏反应的假设。结肠敏感性是通过监测在无害的结肠扩张水平(30毫米汞柱)期间的内脏运动行为反应来确定的。在高度焦虑的WKY大鼠中，我们发现安塔拉明(20 mg kg(-1)，i.p.)显著降低大肠扩张引起的内脏运动反应。在第二项研究中，中央管理(i.c.v.)用CRF诱导低焦虑Fischer 344(F-344)大鼠结肠超敏反应，在该模型中，安塔拉明可显著抑制CRF诱导的结肠超敏反应。总之，选择性CRF受体拮抗剂antalarmin可以抑制中枢应用CRF的WKY大鼠或F-344大鼠的结肠超敏反应。我们的发现提示CRF受体拮抗剂可能是治疗IBS的一种新的治疗方法。
The potential relationship between stress and irritable bowel syndrome (IBS) symptomatology suggests a possible role for stress-mediating hormones, such as corticotropin-releasing factor (CRF), in the altered perception of stimuli in IBS patients. In previous studies, Wistar-Kyoto (WKY) rats with genetic indices of high anxiety demonstrated colonic hypersensitivity coupled with a high basal level of CRF within the central nervous system. In the current study we tested the hypothesis that a selective, non-peptide CRF, receptor antagonist, antalarmin, would inhibit hypersensitivity in the WKY rat colon. Colonic sensitivity was determined by monitoring a visceromotor behavioural response during innocuous levels of colorectal distention (30 mmHg). In high anxiety WKY rats we found that antalarmin (20 mg kg(-1), i.p.) significantly decreased the visceromotor response induced by colorectal distention. In a second study central administration (i.c.v.) of CRF was used to induce colonic hypersensitivity in lower anxiety Fischer 344 (F-344) rats, and in this model, antalarmin significantly inhibited the CRF-induced colonic hypersensitivity. In summary, a selective CRF, receptor antagonist, antalarmin, inhibits colonic hypersensitivity apparent in WKY rats or in F-344 rats given a central administration of CRF. Our findings suggest that CRF, receptor antagonism may represent a novel therapeutic approach for the treatment of IBS.