Taché Y, Perdue M H
CURE/Digestive Diseases Research Center and Center for Neurovisceral Sciences and Womens' Health, West Los Angeles VA, USA.
Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:137-42. doi: 10.1111/j.1743-3150.2004.00490.x.
Central corticotrophin releasing-factor (CRF) signalling pathways are involved in the endocrine, behavioural and visceral responses to stress. Recent studies indicate that peripheral CRF-related mechanisms also contribute to stress-induced changes in gut motility and intestinal mucosal function. Peripheral injection of CRF or urocortin inhibits gastric emptying and motility through interaction with CRF2 receptors and stimulates colonic transit, motility, Fos expression in myenteric neurones and defecation through activation of CRF1 receptors. With regard to intestinal epithelial cell function, intraperitoneal CRF increases ion secretion and mucosal permeability to macromolecules. The motility and mucosal changes induced by peripheral CRF mimic those induced by acute stress. In addition, CRF receptor antagonists given peripherally prevent acute restraint and water avoidance stress-induced delayed gastric emptying, stimulation of colonic motor function and mucosal permeability. Similarly, early trauma enhanced intestinal mucosal dysfunction to an acute stressor in adult rats and the response is prevented by peripheral injection of CRF antagonist. Chronic psychological stress results in reduced host defence and initiates intestinal inflammation through mast cell-dependent mechanisms. These findings provide convergent evidence that activation of peripheral CRF receptors and mast cells are important mechanisms involved in stress-related alterations of gut physiology.
中枢促肾上腺皮质激素释放因子（CRF）信号通路参与对应激的内分泌、行为和内脏反应。最近的研究表明，外周CRF相关机制也有助于应激诱导的肠道运动和肠黏膜功能变化。外周注射CRF或尿皮质素通过与CRF2受体相互作用抑制胃排空和运动，并通过激活CRF1受体刺激结肠转运、运动、肠肌间神经元中的Fos表达和排便。关于肠上皮细胞功能，腹腔注射CRF会增加离子分泌和黏膜对大分子的通透性。外周CRF诱导的运动和黏膜变化与急性应激诱导的变化相似。此外，外周给予CRF受体拮抗剂可预防急性束缚和禁水应激诱导的胃排空延迟、结肠运动功能刺激和黏膜通透性增加。同样，早期创伤会增强成年大鼠对急性应激源的肠黏膜功能障碍，而外周注射CRF拮抗剂可预防这种反应。慢性心理应激会导致宿主防御能力下降，并通过肥大细胞依赖的机制引发肠道炎症。这些发现提供了一致的证据，表明外周CRF受体和肥大细胞的激活是参与应激相关肠道生理改变的重要机制。
