Trimble N, Johnson A C, Foster A, Greenwood-van Meerveld B
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, OK, USA.
Neurogastroenterol Motil. 2007 Sep;19(9):754-60. doi: 10.1111/j.1365-2982.2007.00951.x.
Corticotropin releasing factor (CRF) is an important mediator in the stress response. Previous studies in rodent models demonstrated that stress-induced colonic hypersensitivity was inhibited by CRF1 receptor antagonism. As CRF(1)R-deficient mice have (+/+), CRF(1)R (+/-) and CRF(1)R (-/-) mice colonic sensitivity was assessed via a visceromotor behavioural response (VMR) induced by colorectal distension (CRD, 0-60 mmHg). In the CRF(1)R (+/+) mice there was a pressure-dependent increase in the VMR to CRD that was moderately attenuated in the CRF1R (+/-) mice. However in the CRF(1)R (-/-) mice a VMR to CRD was only observed at the highest distension pressure (60 mmHg). A CRF(1)R antagonist, NBI 30775 (30 mg kg(-1) i.p.) significantly decreased the VMR to CRD in CRF(1)R +/+ mice. An identical inhibitory effect of NBI 30775 was observed in 43% of the CRF(1)R +/- mice. This study provides pharmacological and genetic evidence for the importance of CRF(1)R in colonic sensitivity and suggests a link between stress and visceral perception.
促肾上腺皮质激素释放因子（CRF）是应激反应中的一种重要介质。先前在啮齿动物模型中的研究表明，CRF1受体拮抗作用可抑制应激诱导的结肠超敏反应。由于CRF(1)R基因缺陷小鼠有野生型（+/+）、杂合子（CRF(1)R +/-）和纯合子（CRF(1)R (-/-)）小鼠，通过结直肠扩张（CRD，0 - 60 mmHg）诱导的内脏运动行为反应（VMR）来评估结肠敏感性。在CRF(1)R（+/+）小鼠中，对CRD的VMR呈压力依赖性增加，在CRF1R（+/-）小鼠中这种增加有所减弱。然而，在CRF(1)R（-/-）小鼠中，仅在最高扩张压力（60 mmHg）时才观察到对CRD的VMR。CRF(1)R拮抗剂NBI 30775（30 mg kg(-1)腹腔注射）显著降低了CRF(1)R +/+小鼠对CRD的VMR。在43%的CRF(1)R +/-小鼠中观察到了NBI 30775相同的抑制作用。这项研究为CRF(1)R在结肠敏感性中的重要性提供了药理学和遗传学证据，并提示了应激与内脏感觉之间的联系。
