尿皮质素
肠神经系统
内科学
肠易激综合征
内分泌学
运动性
受体
胃肠功能
医学
促肾上腺皮质激素释放激素
胃排空
肌间神经丛
生物
胃
细胞生物学
免疫组织化学
作者
Sumei Liu,Jackie D. Wood
出处
期刊:Frontiers of gastrointestinal research
日期:2012-01-01
卷期号:: 115-123
被引量:2
摘要
Stress is associated with the onset, exacerbation, and reactivation of many gastrointestinal disorders, including irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). Corticotropin-releasing factor (CRF) is a neuropeptide that plays a major role in the body’s overall responses to stress, including in the gut. The role of central CRF signaling pathways in stress-induced changes in gut motility has been well characterized. Recent studies suggest that peripheral CRF-related mechanisms also contribute to stress-induced changes in gut motility and intestinal mucosal function. CRF peptides (including CRF, urocortin 1, 2, and 3) and CRF receptors (i.e. CRF1 and CRF2) are present in the gut, especially in the enteric nervous system (ENS). CRF and urocortin 1 increase the excitability of ENS neurons via activation of CRF1 receptors expressed by the neurons. Peripheral administration of CRF or urocortin 1 inhibits gastric emptying and motility through interaction with CRF2 receptors in the stomach and stimulates colonic transit, motility and defecation via activation of CRF1 receptors in the large intestine. The changes in gastrointestinal motility induced by peripheral CRF or urocortin 1 mimic those induced by acute stress. Moreover, peripheral injection of CRF receptor antagonists, which do not cross the blood-brain barrier, prevents acute stress-induced delayed gastric emptying and stimulation of colonic motor function. Acute stress, peripheral CRF and the selective CRF1 receptor agonist increase the excitability of neurons in the colonic myenteric plexus. Acute and chronic stress increase intestinal ion secretion and mucosal permeability to macromolecules and cause diarrhea. Effects of stress on intestinal mucosal function are mimicked by peripheral injection of CRF and are suppressed by peripheral injection of nonselective peptide CRF receptor antagonists. Findings of this nature are strong evidence that activation of peripheral CRF receptors in the ENS is an important mechanism involved in stress-related alterations of gut motility and mucosal function.
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