Gibbons Simon J, Farrugia Gianrico
Enteric Neuroscience Program, Mayo Clinic Rochester, 200 First Street SW, Rochester MN 55905, USA.
J Physiol. 2004 Apr 15;556(Pt 2):325-36. doi: 10.1113/jphysiol.2003.056556. Epub 2004 Feb 6.
Carbon monoxide (CO) is a biologically active product of haem metabolism that contributes to the normal physiology of the gastrointestinal tract. In this article, we review recent data showing that CO is an integral regulator of gastrointestinal motility and an important factor in the response to gastrointestinal injury. CO is generated by haem oxygenase-2 (HO-2), which is constitutively expressed in many inhibitory neurones of the vertebrate enteric nervous system. The membrane potential gradients along and across the muscle layers of the gastrointestinal tract require the generation of CO by haem oxygenase-2. The presence of CO is also necessary for normal inhibitory neurotransmission in circular smooth muscle and appears to permit nitric oxide-mediated inhibitory neurotransmission. Genetic deletion of the haem oxygenase-2 gene in mice slows gut transit. The other major CO synthetic enzyme, haem oxygenase-1 (HO-1) is induced under conditions of stress or injury. Recent studies have demonstrated that up-regulation of haem oxygenase-1 protects the gut from several types of gastrointestinal injury, suggesting that CO or induction of HO-1 may find therapeutic use in gastrointestinal diseases and injuries. Furthermore, it is anticipated that the understanding of CO-mediated signalling in the gastrointestinal tract will inform studies in other tissues that express haem oxygenases.
一氧化碳（CO）是血红素代谢的生物活性产物，对胃肠道的正常生理功能有贡献。在本文中，我们综述了近期数据，这些数据表明CO是胃肠动力的一个不可或缺的调节因子，也是对胃肠道损伤作出反应的一个重要因素。CO由血红素加氧酶-2（HO-2）生成，HO-2在脊椎动物肠神经系统的许多抑制性神经元中组成性表达。沿胃肠道肌层及跨肌层的膜电位梯度需要HO-2生成CO。CO的存在对于环形平滑肌中的正常抑制性神经传递也是必需的，并且似乎允许一氧化氮介导的抑制性神经传递。小鼠中血红素加氧酶-2基因的基因缺失会减缓肠道运输。另一种主要的CO合成酶，即血红素加氧酶-1（HO-1），在应激或损伤条件下被诱导。近期研究表明，HO-1的上调可保护肠道免受几种类型的胃肠道损伤，这表明CO或HO-1的诱导可能在胃肠道疾病和损伤的治疗中得到应用。此外，预计对胃肠道中CO介导的信号传导的理解将为其他表达血红素加氧酶的组织的研究提供信息。
