Zakhary R, Poss K D, Jaffrey S R, Ferris C D, Tonegawa S, Snyder S H
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14848-53. doi: 10.1073/pnas.94.26.14848.
Neuronal nitric oxide synthase (nNOS) generates NO in neurons, and heme-oxygenase-2 (HO-2) synthesizes carbon monoxide (CO). We have evaluated the roles of NO and CO in intestinal neurotransmission using mice with targeted deletions of nNOS or HO-2. Immunohistochemical analysis demonstrated colocalization of nNOS and HO-2 in myenteric ganglia. Nonadrenergic noncholinergic relaxation and cyclic guanosine 3',5' monophosphate elevations evoked by electrical field stimulation were diminished markedly in both nNOSDelta/Delta and HO-2(Delta)/Delta mice. In wild-type mice, NOS inhibitors and HO inhibitors partially inhibited nonadrenergic noncholinergic relaxation. In nNOSDelta/Delta animals, NOS inhibitors selectively lost their efficacy, and HO inhibitors were inactive in HO-2(Delta)/Delta animals.
神经元型一氧化氮合酶（nNOS）在神经元中生成一氧化氮（NO），而血红素加氧酶-2（HO-2）合成一氧化碳（CO）。我们利用nNOS或HO-2基因靶向缺失的小鼠，评估了NO和CO在肠道神经传递中的作用。免疫组织化学分析显示，nNOS和HO-2在肌间神经节中共定位。电场刺激诱发的非肾上腺素能非胆碱能舒张以及环磷酸鸟苷升高在nNOSΔ/Δ和HO-2（Δ）/Δ小鼠中均显著减弱。在野生型小鼠中，一氧化氮合酶抑制剂和HO抑制剂可部分抑制非肾上腺素能非胆碱能舒张。在nNOSΔ/Δ动物中，一氧化氮合酶抑制剂选择性地失去了其效力，而HO抑制剂在HO-2（Δ）/Δ动物中则无活性。
