Rhythmic changes in colonic motility are regulated by period genes
Rhythmic changes in colonic motility are regulated by period genes
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DOI：
10.1152/ajpgi.00402.2009
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发表时间：
2010-02-01
影响因子：
4.5
通讯作者：
Cassone, Vincent M.
中科院分区：
文献类型：
--
作者：
Hoogerwerf, Willemijntje A.;Shahinian, Vahakn B.;Cassone, Vincent M.
人类的肠道运动通常发生在白天，很少发生在夜间，这表明生物钟在调节结肠运动中起着重要作用。研究揭示了大脑生物钟功能的分子和生理机制；对外周节律性的了解较少。本研究旨在确定时钟基因如周期1 （per1）和周期2 （per2）是否调节结肠运动的节律变化。器官浴研究、结肠内压力测量和粪便研究用于检测野生型和per1per2双敲除小鼠的结肠运动。为了进一步研究圆形肌肉收缩性节律性变化的机制，我们在神经性一氧化氮合酶（nNOS）敲除小鼠中完成了进一步的研究。在体内的结肠内压力变化和粪便排出量，以及在体外的结肠循环肌收缩力都是有节律的，在夜间开始时活动最大。相比之下，在per1per2双敲除小鼠中，这些测量没有节律性。n - ω -硝基- l -精氨酸甲酯存在时，野生型小鼠和nNOS敲除小鼠的结肠循环肌收缩性也被消除。这些发现表明结肠运动的节律受时钟基因和nnos介导的抑制过程的调节，并表明这两种机制之间存在联系。
Human bowel movements usually occur during the day and seldom during the night, suggesting a role for a biological clock in the regulation of colonic motility. Research has unveiled molecular and physiological mechanisms for biological clock function in the brain; less is known about peripheral rhythmicity. This study aimed to determine whether clock genes such as period 1 (per1) and period2 (per2) modulate rhythmic changes in colonic motility. Organ bath studies, intracolonic pressure measurements, and stool studies were used to examine measures of colonic motility in wild-type and per1per2 double-knockout mice. To further examine the mechanism underlying rhythmic changes in circular muscle contractility, additional studies were completed in neuronal nitric oxide synthase (nNOS) knockout mice. Intracolonic pressure changes and stool output in vivo, and colonic circular muscle contractility ex vivo, are rhythmic with greatest activity at the start of night in nocturnal wild-type mice. In contrast, rhythmicity in these measures was absent in per1per2 double-knockout mice. Rhythmicity was also abolished in colonic circular muscle contractility of wild-type mice in the presence of N-omega-nitro-L-arginine methyl ester and in nNOS knockout mice. These findings suggest that rhythms in colonic motility are regulated by both clock genes and a nNOS-mediated inhibitory process and suggest a connection between these two mechanisms.