Distribution and function of monoacylglycerol lipase in the gastrointestinal tract
Distribution and function of monoacylglycerol lipase in the gastrointestinal tract
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DOI：
10.1152/ajpgi.90500.2008
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发表时间：
2008-12-01
影响因子：
4.5
通讯作者：
Sharkey, Keith A.
中科院分区：
文献类型：
--
作者：
Duncan, Marnie;Thomas, Adam D.;Sharkey, Keith A.
内源性大麻素系统在健康和疾病的胃肠功能调节中起着重要作用。内源性大麻素水平受分解代谢酶调节。在这里，我们描述的存在和定位的单酰基甘油脂肪酶（MGL），负责2-花生四烯酸甘油的降解的主要酶。我们使用分子，生物化学，免疫组织化学和功能测定来表征MGL的分布和活性。MGL mRNA存在于大鼠回肠整个肠壁中。MGL蛋白分布在回肠的肌肉和粘膜层以及十二指肠、近端结肠和远端结肠中。我们观察到MGL在肠神经系统的神经细胞体和神经纤维中的表达。有广泛的MGL与PGP 9.5和calretinin免疫反应神经元，但不与一氧化氮合酶的共定位。MGL也存在于上皮中，并在小肠中高度表达。酶活性水平在十二指肠中最高，沿肠道沿着降低，在远端结肠中最低。我们观察到可溶性和膜相关的酶活性。MGL抑制剂URB 602显著抑制小鼠的全肠转运，这一作用在大麻素1受体缺陷小鼠中被消除。总之，MGL是本地化的肠神经系统，内源性大麻素调节肠蠕动。MGL在上皮细胞中高度表达，这种酶可能具有消化或其他功能，但尚未确定。
The endogenous cannabinoid system plays an important role in the regulation of gastrointestinal function in health and disease. Endocannabinoid levels are regulated by catabolic enzymes. Here, we describe the presence and localization of monoacylglycerol lipase (MGL), the major enzyme responsible for the degradation of 2-arachidonoylglycerol. We used molecular, biochemical, immunohistochemical, and functional assays to characterize the distribution and activity of MGL. MGL mRNA was present in rat ileum throughout the wall of the gut. MGL protein was distributed in the muscle and mucosal layers of the ileum and in the duodenum, proximal colon, and distal colon. We observed MGL expression in nerve cell bodies and nerve fibers of the enteric nervous system. There was extensive colocalization of MGL with PGP 9.5 and calretinin-immunoreactive neurons, but not with nitric oxide synthase. MGL was also present in the epithelium and was highly expressed in the small intestine. Enzyme activity levels were highest in the duodenum and decreased along the gut with lowest levels in the distal colon. We observed both soluble and membrane-associated enzyme activities. The MGL inhibitor URB602 significantly inhibited whole gut transit in mice, an action that was abolished in cannabinoid 1 receptor-deficient mice. In conclusion, MGL is localized in the enteric nervous system where endocannabinoids regulate intestinal motility. MGL is highly expressed in the epithelium, where this enzyme may have digestive or other functions yet to be determined.