Fatty acid amide hydrolase controls mouse intestinal motility in vivo
Fatty acid amide hydrolase controls mouse intestinal motility in vivo
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DOI：
10.1053/j.gastro.2005.06.018
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发表时间：
2005-09-01
期刊：
影响因子：
29.4
通讯作者：
Izzo, AA
中科院分区：
文献类型：
--
作者：
Capasso, R;Matias, I;Izzo, AA
背景和目的：脂肪酸酰胺水解酶 (FAAH) 催化内源性大麻素（已知会抑制肠道蠕动）和其他生物活性酰胺（棕榈酰乙醇酰胺、油酰胺和油酰乙醇酰胺）的水解，这可能会影响肠道蠕动。 FAAH 在肠道中的生理作用很大程度上尚未被探索。在本研究中，我们评估了 FAAH 在体内调节小鼠肠道蠕动方面的可能作用。方法：通过评估荧光标记物沿小肠的分布来测量运动性；通过逆转录聚合酶链式反应 (RT-PCR) 分析 FAAH 信使 RNA (mRNA) 水平；通过同位素稀释、液相色谱、质谱法测量内源性大麻素水平。结果：运动受到 N-花生四烯酰血清素 (AA-5-HT) 和棕榈酰异丙酰胺（2 种选择性 FAAH 抑制剂）以及 FAAH 底物棕榈酰乙醇酰胺、油酰胺和油酰乙醇酰胺的抑制。 CB1 降低了 AA-5-HT 的作用。受体拮抗剂 Rimon-abant 和小鼠体内 CB:L 缺陷所致，但不是香草素受体拮抗剂 5'-碘树脂毒素所致。在 FAAH 缺陷小鼠中，FAAH 的药物阻断并不影响肠道蠕动。在肠道的不同区域检测到FAAH mRNA。结论：我们得出结论，FAAH 是肠道蠕动的生理调节剂，也是开发能够减少肠道蠕动的药物的潜在靶点。
Background & Aims: Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis both of the endocannabinoids (which are known to inhibit intestinal motility) and other bioactive amides (palmitoylethanolamide, oleamide, and oleoylethanolamide), which might affect intestinal motility. The physiologic role of FAAH in the gut is largely unexplored. In the present study, we evaluated the possible role of FAAH in regulating intestinal motility in mice in vivo. Methods: Motility was measured by evaluating the distribution of a fluorescent marker along the small intestine; FAAH messenger RNA (mRNA) levels were analyzed by reverse-transcription polymerase chain reaction (RT-PCR); endocannabinoid levels were measured by isotope-dilution, liquid chromatography, mass spectrometry. Results: Motility was inhibited by N-arachidonoylserotonin (AA-5-HT) and palmitoylisopropylamide, 2 selective FAAH inhibitors, as well as by the FAAH substrates palmitoylethanolamide, oleamide, and oleoylethanolamide. The effect of AA-5-HT was reduced by the CB1. receptor antagonist rimon-abant and by CB:L deficiency in mice but not by the vanilloid receptor antagonist 5'-iodoresiniferatoxin. In FAAH-deficient mice, pharmacologic blockade of FAAH did not affect intestinal motility. FAAH mRNA was detected in different regions of the intestinal tract. Conclusions: We conclude that FAAH is a physiologic regulator of intestinal motility and a potential target for the development of drugs capable of reducing intestinal motility.