Small intestinal motility in soluble guanylate cyclase α1 knockout mice
Small intestinal motility in soluble guanylate cyclase α1 knockout mice
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DOI：
10.1007/s00210-008-0380-x
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发表时间：
2009-05-01
影响因子：
3.6
通讯作者：
Lefebvre, Romain A.
中科院分区：
文献类型：
--
作者：
Dhaese, Ingeborg;Vanneste, Gwen;Lefebvre, Romain A.
一氧化氮（NO）激活可溶性鸟苷酸环化酶（sGC）生成鸟苷-3′，5′-环-单磷酸鸟苷（cGMP）。本研究的目的是探讨sGC α(1)敲除（KO）小鼠空肠运动的氮能调节。在圆形肌条中测定对氮能刺激的功能反应和对氮能刺激的cGMP水平。测定肠道运输。电场刺激和外源NO诱导的氮能松弛在雄性KO条中几乎被消除，而在雌性KO条中仅轻微减弱并对ODQ敏感。KO条带的基础cGMP水平降低，但NO仍诱导cGMP水平升高。在雄性和雌性KO小鼠中，转运均未减弱。在体外实验中，sGC α (1) β(1)是空肠氮能松弛最重要的亚型，但氮能松弛也可以通过sGC α (2) β(1)的激活而发生。后一种机制在雌性KO小鼠中比在雄性KO小鼠中更为明显。在体内，在雄性和雌性KO小鼠中没有观察到对肠道运动的重要影响。
Nitric oxide (NO) activates soluble guanylate cyclase (sGC) to produce guanosine-3',5'-cyclic-monophosphate (cGMP). The aim of this study was to investigate the nitrergic regulation of jejunal motility in sGC alpha(1) knockout (KO) mice. Functional responses to nitrergic stimuli and cGMP levels in response to nitrergic stimuli were determined in circular muscle strips. Intestinal transit was determined. Nitrergic relaxations induced by electrical field stimulation and exogenous NO were almost abolished in male KO strips, but only minimally reduced and sensitive to ODQ in female KO strips. Basal cGMP levels were decreased in KO strips, but NO still induced an increase in cGMP levels. Transit was not attenuated in male nor female KO mice. In vitro, sGC alpha(1)beta(1) is the most important isoform in nitrergic relaxation of jejunum, but nitrergic relaxation can also occur via sGC alpha(2)beta(1) activation. The latter mechanism is more pronounced in female than in male KO mice. In vivo, no important implications on intestinal motility were observed in male and female KO mice.