Lee Yunna, Jo Jeongbin, Chung Hae Young, Pothoulakis Charalabos, Im Eunok
College of Pharmacy, Pusan National University, Busan, Korea; and.
Section of Inflammatory Bowel Disease & Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California.
Am J Physiol Gastrointest Liver Physiol. 2016 Oct 1;311(4):G655-G666. doi: 10.1152/ajpgi.00294.2015. Epub 2016 Aug 18.
The endocannabinoid system mainly consists of endogenously produced cannabinoids (endocannabinoids) and two G protein-coupled receptors (GPCRs), cannabinoid receptors 1 and 2 (CB and CB). This system also includes enzymes responsible for the synthesis and degradation of endocannabinoids and molecules required for the uptake and transport of endocannabinoids. In addition, endocannabinoid-related lipid mediators and other putative endocannabinoid receptors, such as transient receptor potential channels and other GPCRs, have been identified. Accumulating evidence indicates that the endocannabinoid system is a key modulator of gastrointestinal physiology, influencing satiety, emesis, immune function, mucosal integrity, motility, secretion, and visceral sensation. In light of therapeutic benefits of herbal and synthetic cannabinoids, the vast potential of the endocannabinoid system for the treatment of gastrointestinal diseases has been demonstrated. This review focuses on the role of the endocannabinoid system in gut homeostasis and in the pathogenesis of intestinal disorders associated with intestinal motility, inflammation, and cancer. Finally, links between gut microorganisms and the endocannabinoid system are briefly discussed.
内源性大麻素系统主要由内源性产生的大麻素(内源性大麻素)和两种G蛋白偶联受体(GPCR),即大麻素受体1和2(CB1和CB2)组成。该系统还包括负责内源性大麻素合成和降解的酶以及内源性大麻素摄取和运输所需的分子。此外,还鉴定出了与内源性大麻素相关的脂质介质和其他假定的内源性大麻素受体,如瞬时受体电位通道和其他GPCR。越来越多的证据表明,内源性大麻素系统是胃肠生理学的关键调节因子,影响饱腹感、呕吐、免疫功能、粘膜完整性、运动性、分泌和内脏感觉。鉴于草药和合成大麻素的治疗益处,内源性大麻素系统在治疗胃肠道疾病方面的巨大潜力已得到证实。本综述重点关注内源性大麻素系统在肠道稳态以及与肠道运动、炎症和癌症相关的肠道疾病发病机制中的作用。最后,简要讨论了肠道微生物与内源性大麻素系统之间的联系。